references.bib

@inbook{Colleluori2022,
	title = {Brown Fat Anatomy in Humans and Rodents},
	author = {Colleluori, Georgia and Perugini, Jessica and Di Vincenzo, Angelica and Senzacqua, Martina and Giordano, Antonio and Cinti, Saverio},
	year = {2022},
	date = {2022},
	publisher = {Springer US},
	pages = {19--42},
	doi = {10.1007/978-1-0716-2087-8_2},
	url = {http://dx.doi.org/10.1007/978-1-0716-2087-8_2},
	langid = {en}
}

@article{Foster1978,
   abstract = {Measurements with tracer microspheres of changes in tissue blood flow associated with noradrenaline (NA)-induced calorigenesis in warm-acclimated and in cold-acclimated (CA) rats revealed very large increases in flow to brown adipose tissue (BAT). The data on flow together with measurements of the arteriovenous difference in blood O2 across interscapular BAT indicate that BAT accounts for at least 60% of the NA-induced nonshivering thermogenesis (NST) of CA rats. Skeletal muscle was found to be only minimally, if at all, involved in this NST.},
   author = {D. O. Foster and M. L. Frydman},
   doi = {10.1007/978-3-0348-5559-4_16},
   issn = {0071-335X},
   journal = {Experientia. Supplementum},
   keywords = {Acclimatization,Adipose Tissue,Animals,Body Temperature Regulation* / drug effects,Brown / blood supply,Brown / drug effects,Brown / physiology*,Cold Temperature,D O Foster,Hot Temperature,M L Frydman,MEDLINE,Muscles / blood supply,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Norepinephrine / pharmacology,Oxygen / blood,PubMed Abstract,Rats,Regional Blood Flow / drug effects,doi:10.1007/978-3-0348-5559-4_16,pmid:274305},
   pages = {147-151},
   pmid = {274305},
   publisher = {Experientia Suppl},
   title = {Brown adipose tissue: the dominant site of nonshivering thermogenesis in the rat},
   volume = {32},
   url = {https://pubmed.ncbi.nlm.nih.gov/274305/},
   year = {1978},
}

@article{BARRAND1984,
   abstract = {Amine oxidase activity, previously described in homogenates of brown adipose tissue of the rat, has now been investigated in preparations of isolated fat cells. It was found that the specific activities of both monoamine oxidase A (MAO) and of the semicarbazide‐sensitive clorgyline‐resistant amine oxidase (SSAO) were higher in isolated fat cells than in the original whole tissue. Brown adipocytes therefore represent a major source of both these enzymes. In plasma membranes prepared from these isolated brown fat cells by borate extraction there was a similar enrichment of activity of SSAO and of the plasma membrane marker enzyme, phosphodiesterase I. However in preparations of cell membranes made by binding the cells to polycation‐coated beads, enrichment of phosphodiesterase I activity was much greater than that of SSAO. It is suggested that the disposition of the enzyme within the cell membrane may account for the discrepancy in these results, i.e. the sidedness of the membrane may be important. Histochemical visualization of enzyme activity in whole tissue at the ultrastructural level was undertaken. Positive staining of mitochondria was achieved in the presence of the MAO substrate, tryptamine. Staining around the edges of the brown fat cells was observed with the SSAO substrates, tyramine and benzylamine. Staining was largely absent when substrate was omitted or after pretreatment with the irreversible SSAO inhibitor, hydralazine and the slowly reversible inhibitor, semicarbazide. It is not definitely proven that this staining represents sites of enzyme activity but the results are consistent with evidence from other studies indicating that SSAO in brown adipose tissue of the rat may be found predominantly at the fat cell surface. The significance of these findings in relation to the possible function of SSAO is discussed. 1984 Royal Pharmaceutical Society of Great Britain},
   author = {MARGERY A. BARRAND and SHEILA A. FOX and BRIAN A. CALLINGHAM},
   doi = {10.1111/j.2042-7158.1984.tb04837.x},
   issn = {20427158},
   issue = {10},
   journal = {Journal of Pharmacy and Pharmacology},
   pages = {652-658},
   pmid = {6150080},
   title = {Amine oxidase activities in brown adipose tissue of the rat: identification of semicarbazide‐sensitive (clorgyline‐resistant) activity at the fat cell membrane},
   volume = {36},
   year = {1984},
}

@article{Barrant1984,
   author = {M. A. Barrant and B. A. Callingham},
   doi = {10.1042/BJ2220467},
   issn = {0264-6021},
   issue = {2},
   journal = {The Biochemical journal},
   keywords = {Adipose Tissue,Affinity,Amine Oxidase (Copper-Containing)*,Animals,B A Callingham,Benzylamines / metabolism,Brown / enzymology*,Brown / radiation effects,Cell Membrane / enzymology,Chromatography,Gel,In Vitro Techniques,Inbred Strains,Kinetics,M A Barrand,MEDLINE,Male,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,Octoxynol,Oxidoreductases Acting on CH-NH Group Donors / antagonists & inhibitors,Oxidoreductases Acting on CH-NH Group Donors / isolation & purification,Oxidoreductases Acting on CH-NH Group Donors / metabolism*,PMC1144201,Polyethylene Glycols,PubMed Abstract,Rats,Research Support,Semicarbazides / pharmacology,Solubility,doi:10.1042/bj2220467,pmid:6477528},
   pages = {467-475},
   pmid = {6477528},
   publisher = {Biochem J},
   title = {Solubilization and some properties of a semicarbazide-sensitive amine oxidase in brown adipose tissue of the rat},
   volume = {222},
   url = {https://pubmed.ncbi.nlm.nih.gov/6477528/},
   year = {1984},
}

@article{Lyles1995,
   abstract = {Although the existence of a membrane-bound (probably plasmalemmal) semicarbazide-sensitive amine oxidase (SSAO) is well established in various mammalian tissues, and especially within vascular smooth muscle, its importance and the possible consequences of its metabolism of certain physiological and xenobiotic amines in vivo are under continuing investigation. In this respect, there are major species-related differences in substrate specificity determined in vitro, not only towards the synthetic amine benzylamine, but also towards some other aromatic amines (e.g. tyramine, tryptamine, 2-phenylethylamine, dopamine, histamine) which are possible endogenous substrates. Inhibition of SSAO can potentiate the pharmacological activity of some amines in isolated tissue (e.g. blood vessel) preparations from some species. Recent evidence has accumulated that SSAO may also be involved in metabolizing endogenous aliphatic amines such as methylamine and aminoacetone, focussing attention on the fact that the aldehyde products (formaldehyde and methylglyoxal, respectively) are potentially cytotoxic agents. Indeed, SSAO has been implicated in experimental models of cardiovascular toxicity involving conversion of the industrial aliphatic amine allylamine to acrolein. In summary, metabolism by SSAO may reduce the physiological/pharmacological effects of some amines, but the resulting metabolites (aldehydes, H2O2) may also have important actions.},
   author = {G. A. Lyles},
   doi = {10.1016/s0079-6123(08)61226-1},
   issn = {00796123},
   journal = {Progress in Brain Research},
   pages = {293-303},
   pmid = {8584666},
   publisher = {Elsevier B.V.},
   title = {Substrate-specificity of mammalian tissue-bound semicarbazide-sensitive amine oxidase},
   volume = {106},
   year = {1995},
}

@article{Garpenstrand2004,
   abstract = {Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme associated with vascular systems in mammals. SSAO catalyzes the deamination of primary monoamines and has been suggested to be a risk factor in vascular disorders, e.g., diabetic vascular complications. The primary aim of the present study was to investigate if serum SSAO activity is associated with clinical parameters in non-small cell lung cancer (NSCLC) patients. Secondary aims were to investigate if there is a correlation between SSAO activity and the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Thirty-three patients donated 231 serum samples. Detectable levels of bFGF, VEGF, and SSAO were observed in all patients. Serum SSAO activity was not statistically associated with survival (p = 0.35). A highly significant statistical correlation was found between SSAO activity and VEGF (p < 0.0001). No significant correlation between SSAO and bFGF was observed. We conclude that SSAO was not associated with survival in patients with NSCLC. However, a strong correlation between serum SSAO activity and the angiogenic factor VEGF was found that might implicate new aspects of the mechanisms controlling angiogenesis.},
   author = {Håkan Garpenstrand and Michael Bergqvist and Daniel Brattström and Anders Larsson and Lars Oreland and Patrik Hesselius and Gunnar Wagenius},
   doi = {10.1385/MO:21:3:241/METRICS},
   issn = {13570560},
   issue = {3},
   journal = {Medical Oncology},
   keywords = {Angiogenesis,Basic fibroblast growth factor (bFGF),Non-small cell lung cancer,SSAO,Vascular endothelial growth factor (VEGF)},
   pages = {241-250},
   pmid = {15456951},
   publisher = {Springer},
   title = {Serum semicarbazide-sensitive amine oxidase (SSAO) activity correlates with VEGF in non-small-cell lung cancer patients},
   volume = {21},
   url = {https://link.springer.com/article/10.1385/MO:21:3:241},
   year = {2004},
}
@article{Unzeta2021,
   abstract = {The semicarbazide-sensitive amine oxidase (SSAO), also known as vascular adhesion protein-1 (VAP-1) or primary amine oxidase (PrAO), is a deaminating enzyme highly expressed in vessels that generates harmful products as a result of its enzymatic activity. As a multifunctional enzyme, it is also involved in inflammation through its ability to bind and promote the transmigration of circulating leukocytes into inflamed tissues. Inflammation is present in different systemic and cerebral diseases, including stroke and Alzheimer’s disease (AD). These pathologies show important affectations on cerebral vessels, together with increased SSAO levels. This review summarizes the main roles of SSAO/VAP-1 in human physiology and pathophysiology and discusses the mechanisms by which it can affect the onset and progression of both stroke and AD. As there is an evident interrelationship between stroke and AD, basically through the vascular system dysfunction, the possibility that SSAO/VAP-1 could be involved in the transition between these two pathologies is suggested. Hence, its inhibition is proposed to be an interesting therapeutical approach to the brain damage induced in these both cerebral pathologies.},
   author = {Mercedes Unzeta and Mar Hernàndez-Guillamon and Ping Sun and Montse Solé},
   doi = {10.3390/IJMS22073365},
   issn = {1422-0067},
   issue = {7},
   journal = {International Journal of Molecular Sciences 2021, Vol. 22, Page 3365},
   keywords = {1,Alzheimer’s disease,SSAO/VAP,blood,brain barrier dysfunction,inflammation,neurovascular unit,oxidative stress,stroke,vascular damage},
   month = {3},
   pages = {3365},
   pmid = {33805974},
   publisher = {Multidisciplinary Digital Publishing Institute},
   title = {SSAO/VAP-1 in Cerebrovascular Disorders: A Potential Therapeutic Target for Stroke and Alzheimer’s Disease},
   volume = {22},
   url = {https://www.mdpi.com/1422-0067/22/7/3365/htm https://www.mdpi.com/1422-0067/22/7/3365},
   year = {2021},
}
@article{Lyles1998,
   abstract = {The demonstration of semicarbazide-sensitive amine oxidase (SSAO) activity in some freshly-dispersed cell preparations and in particular types of cells grown in culture, provides increasing opportunities for investigating the importance of SSAO in various aspects of...},
   author = {G. A. Lyles and R. Pino},
   doi = {10.1007/978-3-7091-6499-0_23},
   isbn = {978-3-7091-6499-0},
   issn = {03036995},
   issue = {52},
   journal = {Journal of Neural Transmission, Supplement},
   pages = {239-250},
   pmid = {9564623},
   publisher = {Springer, Vienna},
   title = {Properties and functions of tissue-bound semicarbazide-sensitive amine oxidases in isolated cell preparations and cell cultures},
   url = {https://link.springer.com/chapter/10.1007/978-3-7091-6499-0_23},
   year = {1998},
}
@article{Colleluori2022,
   abstract = {The Brown Adipose Tissue (BAT) is composed by mitochondrial rich, multilocular adipocytes, in strict topographical and functional relation with vasculature and noradrenergic nerves. Brown adipocytes are able to dissipate energy to produce heat, in a process known as non-shivering thermogenesis. Due to its contribution to energy expenditure, BAT is intensely studied for its potential to counteract metabolic diseases such as obesity, type 2 diabetes, dyslipidemia and cardiovascular diseases. BAT displays specific morphological characteristics that allow to assess its functional state. In this chapter we describe methodologies to properly dissect BAT depots, evaluate their gross anatomy, and assess its activation by light microscopy using peroxidase immunostaining and by laser scanning confocal microscopy using immunofluorescence. We also describe methodologies to study BAT ultrastructure by transmission and scanning electron microscopy, to visualize peroxidase immunostaining reactions at an ultrastructural level and to perform immunofluorescence reactions on paraffin-embedded samples, more often available in the clinical setting (due to the possibility to store them long-term) as opposed to fresh samples. The described techniques can be employed to study BAT morphology and activation in response to various stimuli (e.g., cold exposure; specific dietary composition) and in different pathological conditions (e.g., obesity; type 2 diabetes).},
   author = {Georgia Colleluori and Jessica Perugini and Angelica Di Vincenzo and Martina Senzacqua and Antonio Giordano and Saverio Cinti},
   doi = {10.1007/978-1-0716-2087-8_2},
   issn = {1940-6029},
   journal = {Methods in molecular biology (Clifton, N.J.)},
   keywords = {Adipocytes,Adipose Tissue,Animals,Brown,Brown* / metabolism,Diabetes Mellitus,Energy Metabolism,Georgia Colleluori,Humans,Jessica Perugini,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PubMed Abstract,Rodentia,Saverio Cinti,Thermogenesis,Type 2* / metabolism,doi:10.1007/978-1-0716-2087-8_2,pmid:35167088},
   pages = {19-42},
   pmid = {35167088},
   publisher = {Methods Mol Biol},
   title = {Brown Fat Anatomy in Humans and Rodents},
   volume = {2448},
   url = {https://pubmed.ncbi.nlm.nih.gov/35167088/},
   year = {2022},
}
@article{Guo2018,
   abstract = {Brown adipose tissue (BAT) has been identified as a promising target for the treatment of obesity, diabetes, and relevant metabolism disorders because of the adaptive thermogenesis ability of this tissue. Visualizing BAT may provide an essential tool for pathology study, drug screening, and efficacy evaluation. Owing to limitations of current nuclear and magnetic resonance imaging approaches for BAT detection, fluorescence imaging has advantages in large-scale preclinical research on small animals. Here, fast BAT imaging in mice is conducted based on polymer dots as fluorescent probes. As early as 5 min after the intravenous injection of polymer dots, extensive fluorescence is detected in the interscapular BAT and axillar BAT. In addition, axillar and inguinal white adipose tissues (WAT) are recognized. The real-time in vivo behavior of polymer dots in rodents is monitored using the probe-based confocal laser endomicroscopy imaging, and the preferred accumulation in BAT over WAT is confirmed by histological assays. Moreover, the whole study is conducted without a low temperature or pharmaceutical stimulation. The imaging efficacy is verified at the cellular, histological, and whole-body levels, and the present results indicate that fluorescent polymer dots may be a promising tool for the visualization of BAT in living subjects. ©},
   author = {Yixiao Guo and Yao Li and Yidian Yang and Shiyi Tang and Yufan Zhang and Liqin Xiong},
   doi = {10.1021/ACSAMI.8B06094/SUPPL_FILE/AM8B06094_SI_001.PDF},
   issn = {19448252},
   issue = {24},
   journal = {ACS Applied Materials and Interfaces},
   keywords = {brown adipose tissue,conjugated polymers,in vivo,multi-scale,near-infrared fluorescence imaging,probe-based confocal laser endomicroscopy,uncoupling protein-1},
   month = {6},
   pages = {20884-20896},
   pmid = {29893119},
   publisher = {American Chemical Society},
   title = {Multiscale Imaging of Brown Adipose Tissue in Living Mice/Rats with Fluorescent Polymer Dots},
   volume = {10},
   url = {https://pubs.acs.org/doi/abs/10.1021/acsami.8b06094},
   year = {2018},
}
@article{Jakus2008,
   abstract = {Rats were exposed to cold and then reacclimated at neutral temperature. Changes related to fatty acid and glucose metabolism in brown and white adipose tissues (BAT and WAT) and in muscle were then examined. Of the many proteins involved in the metabolic response, two lipogenic enzymes, acetyl-coenzyme A carboxylase (ACC) and ATP-citrate lyase, were found to play a pervasive role and studied in detail. Expression of the total and phosphorylated forms of both lipogenic enzymes in response to cold increased in BAT but decreased in WAT. Importantly, in BAT, only the phosphorylation of the ACC1 isoenzyme was enhanced, whereas that of ACC2 remained unchanged. The activities of these enzymes and the in vivo rate of FFA synthesis together suggested that WAT supplies BAT with FFA and glucose by decreasing its own synthetic activity. Furthermore, cold increased the glucose uptake of BAT by stimulating the expression of components of the insulin signaling cascade, as observed by the enhanced expression and phosphorylation of Akt and GSK-3. In muscle, these changes were observed only during reacclimation, when serum insulin also increased. Such changes may be responsible for the extreme glycogen accumulation in the BAT of rats reacclimated from cold. Copyright ©2008 by the American Society for Biochemistry and Molecular Biology, Inc.},
   author = {Peter B. Jakus and Attila Sandor and Tamas Janaky and Viktoria Farkas},
   doi = {10.1194/JLR.M700316-JLR200},
   issn = {0022-2275},
   issue = {2},
   journal = {Journal of Lipid Research},
   keywords = {Brown adipose tissue,Insulin signaling,Lipogenic enzymes,Phosphorylation,White adipose tissue},
   month = {2},
   pages = {332-339},
   pmid = {17984485},
   publisher = {Elsevier},
   title = {Cooperation between BAT and WAT of rats in thermogenesis in response to cold, and the mechanism of glycogen accumulation in BAT during reacclimation},
   volume = {49},
   year = {2008},
}
@article{Paulus2019,
   abstract = {Introduction Brown adipose tissue (BAT) is considered as a potential target for combating obesity in humans where active BAT metabolizes glucose and fatty acids as fuel resulting in heat production. Prospective studies in humans have been set up to further study the presence and metabolic activity of BAT mostly using Positron Emission Tomography (PET) imaging in cold-stimulated conditions with the radiolabeled glucose derivative [18F]FDG. However, radiotracers beyond [18F]FDG have been proposed to investigate BAT activity, targeting various aspects of BAT metabolism. It remains questionable which tracer is best suited to detect metabolic BAT activity and to what extent those results correlate with ex vivo metabolic BAT activity. Methods PET and Single Photon Emission Computed Tomography (SPECT) imaging, targeting different aspects of BAT activation such as glucose metabolism, fatty acid metabolism, noradrenergic stimulation, blood perfusion and amino acid transport system, was performed immediately after injection of the tracer in rats under different temperatures: room temperature, acute cold (4 C for 4 h) or acclimated to cold (4 C for 6 h per day during 28 days). Furthermore, Magnetic Resonance Spectroscopy (MRS)-derived BAT temperature was measured in control and cold-acclimated rats. Results At room temperature, only [18F]FDG visualized BAT. Glucose metabolism, fatty acid metabolism, noradrenergic stimulation and blood perfusion showed a clear tracer-dependent twofold increase in BAT uptake upon cold exposure. Only the tracer for the amino acid transport system did not show BAT specific uptake under any of the experimental conditions. MRS demonstrated that cold-acclimated animals had BAT with a stronger heat-production compared to control animals. Conclusion BAT activity following cold exposure in rats was visualized by several tracers, while only [18F]FDG was also able to show BAT activity under non-stimulated conditions (room temperature). The variances in uptake of the different tracers should be taken into account when developing future clinical applications in humans.},
   author = {Andreas Paulus and Petronella A. van Ewijk and Emmani B.M. Nascimento and Marijke De Saint-Hubert and Geert Hendrikx and Andrea Vogg and Ivo Pooters and Melanie Schnijderberg and Joris Vanderlocht and Gerard Bos and Boudewijn Brans and Vera B. Schrauwen-Hinderling and Felix M. Mottaghy and Matthias Bauwens},
   doi = {10.1371/JOURNAL.PONE.0215852},
   issn = {19326203},
   issue = {5},
   journal = {PLoS ONE},
   month = {5},
   pmid = {31091250},
   publisher = {PLOS},
   title = {Characterization of BAT activity in rats using invasive and non-invasive techniques},
   volume = {14},
   url = {/pmc/articles/PMC6519816/ /pmc/articles/PMC6519816/?report=abstract https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519816/},
   year = {2019},
}
@article{Yan2023,
   abstract = {The progress of space science and technology has ushered in a new era for humanity’s exploration of outer space. Recent studies have indicated that the aerospace special environment including microgravity and space radiation poses a significant risk to the health of astronauts, which involves multiple pathophysiological effects on the human body as well on tissues and organs. It has been an important research topic to study the molecular mechanism of body damage and further explore countermeasures against the physiological and pathological changes caused by the space environment. In this study, we used the rat model to study the biological effects of the tissue damage and related molecular pathway under either simulated microgravity or heavy ion radiation or combined stimulation. Our study disclosed that ureaplasma-sensitive amino oxidase (SSAO) upregulation is closely related to the systematic inflammatory response (IL-6, TNF-α) in rats under a simulated aerospace environment. In particular, the space environment leads to significant changes in the level of inflammatory genes in heart tissues, thus altering the expression and activity of SSAO and causing inflammatory responses. The detailed molecular mechanisms have been further validated in the genetic engineering cell line model. Overall, this work clearly shows the biological implication of SSAO upregulation in microgravity and radiation-mediated inflammatory response, providing a scientific basis or potential target for further in-depth investigation of the pathological damage and protection strategy under a space environment.},
   author = {Liben Yan and Chunli Sun and Yaxi Zhang and Peng Zhang and Yu Chen and Yifan Deng and Tianyi Er and Yulin Deng and Zhimin Wang and Hong Ma},
   doi = {10.3390/IJMS24043666/S1},
   issn = {14220067},
   issue = {4},
   journal = {International Journal of Molecular Sciences},
   keywords = {inflammatory response,myocardial damage,semicarbazide-sensitive amine oxidase,simulated aerospace environment},
   month = {2},
   pages = {3666},
   pmid = {36835077},
   publisher = {MDPI},
   title = {The Biological Implication of Semicarbazide-Sensitive Amine Oxidase (SSAO) Upregulation in Rat Systemic Inflammatory Response under Simulated Aerospace Environment},
   volume = {24},
   url = {https://www.mdpi.com/1422-0067/24/4/3666/htm https://www.mdpi.com/1422-0067/24/4/3666},
   year = {2023},
}
@article{Papukashvili2020,
   abstract = {Obesity is a worldwide prevalent metabolic disorder that is associated with diabetes, among many other diseases. Bearing this in mind, prevention and treatment ways need to be improved. Notably, activity of the enzyme semicarbazide-sensitive amine oxidase (SSAO) is found to be elevated in overweight subjects. Moreover, SSAO inhibition has resulted in an increase of histamine activity in adipose tissue and the limitation of body fat. The current review aims to overview the risks of obesity, rationalize the molecular ways of SSAO activity, and outline the strategies of inhibiting upregulated enzyme levels. It describes the differences between SSAO inhibitors and advances the prospective agents. Based on evidence, caffeine is proposed as an effective, safe, and reliable choice to inhibit SSAO activity. Furthermore, the histamine in adipocytes has been associated with SSAO activity. Therefore, it is suggested as one of the key compounds to be studied for obesity management. To conclude, inhibiting SSAO may attenuate weight gain and prevent related diseases.},
   author = {Dimitri Papukashvili and Nino Rcheulishvili and Yulin Deng},
   doi = {10.3390/NU12010184},
   issn = {20726643},
   issue = {1},
   journal = {Nutrients},
   keywords = {Caffeine,Diabetes,Histamine,Obesity,Semicarbazide-sensitive amine oxidase (SSAO)},
   pmid = {31936548},
   publisher = {Multidisciplinary Digital Publishing Institute  (MDPI)},
   title = {Attenuation of Weight Gain and Prevention of Associated Pathologies by Inhibiting SSAO},
   volume = {12},
   url = {/pmc/articles/PMC7019322/ /pmc/articles/PMC7019322/?report=abstract https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019322/},
   year = {2020},
}
@article{Che2012,
   abstract = {Wistar rats were treated with caffeine or 2-bromoethylamine, the effect of caffeine on the activity of semicarbazide-sensitive amine oxidase (SSAO) in rat serum and tissues was studied using various LC-MS methods. Caffeine was found to present in all tissues after administration for 10 days and accumulated for 25 days. The level of caffeine was high in brain and liver, and the SSAO activity in all tissues was found to be inhibited by caffeine. As the concentration of caffeine increased, the SSAO activity decreased. The inhibition ratio was correlated to the levels of caffeine present. We presume that caffeine may treat with SSAO activity associated diseases. © 2012 Elsevier Inc.},
   author = {Baoquan Che and Lin Wang and Zhe Zhang and Yongqian Zhang and Yulin Deng},
   doi = {10.1016/J.NEURO.2012.07.004},
   issn = {0161-813X},
   issue = {5},
   journal = {NeuroToxicology},
   keywords = {Accumulation,Caffeine,Distribution,Inhibitor,SSAO},
   month = {10},
   pages = {1248-1253},
   pmid = {22841599},
   publisher = {Elsevier},
   title = {Distribution and accumulation of caffeine in rat tissues and its inhibition on semicarbazide-sensitive amine oxidase},
   volume = {33},
   year = {2012},
}
@article{Abella2003,
   abstract = {In this study we have explored whether the bifunctional protein semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1) represents a novel target for type 2 diabetes. To this end, Goto-Kakizaki (GK) diabetic rats were treated with the SSAO substrate benzylamine and with low ineffective doses of vanadate previously shown to have antidiabetic effects in streptozotocin-induced diabetic rats. The administration of benzylamine in combination with vanadate in type 2 diabetic rats acutely stimulated glucose tolerance, and the chronic treatment normalized hyperglycemia, stimulated glucose transport in adipocytes, and reversed muscle insulin resistance. Acute in vivo administration of benzylamine and vanadate stimulated skeletal muscle glucose transport, an effect that was also observed in incubated muscle preparations coincubated with adipose tissue explants or with human recombinant SSAO. Acute administration of benzylamine/vanadate also ameliorated insulin secretion in diabetic GK rats, and this effect was also observed in incubated pancreatic islets. In keeping with these observations, we also demonstrate that pancreatic islets express SSAO/VAP-1. As far as mechanisms of action, we have found that benzylamine/vanadate causes enhanced tyrosine phosphorylation of proteins and reduced protein tyrosine phosphatase activity in adipocytes. In addition, incubation of human recombinant SSAO, benzylamine, and vanadate generates peroxovanadium compounds in vitro. Based on these data, we propose that benzylamine/vanadate administration generates peroxovanadium locally in pancreatic islets, which stimulates insulin secretion and also produces peroxovanadium in adipose tissue, activating glucose metabolism in adipocytes and in neighboring muscle. This opens the possibility of using the SSAO/VAP-1 activity as a local generator of protein tyrosine phosphatase inhibitors in antidiabetic therapy.},
   author = {Anna Abella and Luc Marti and Marta Camps and Marc Claret and J. Fernández-Alvarez and Ramon Gomis and Anna Gumà and Nathalie Viguerie and Christian Carpéné and Manuel Palacín and Xavier Testar and Antonio Zorzano},
   doi = {10.2337/DIABETES.52.4.1004},
   issn = {00121797},
   issue = {4},
   journal = {Diabetes},
   month = {4},
   pages = {1004-1013},
   pmid = {12663473},
   title = {Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 activity exerts an antidiabetic action in Goto-Kakizaki rats},
   volume = {52},
   year = {2003},
}
@article{Boomsma2000,
   abstract = {Aims: Experimental evidence has suggested that semicarbazide-sensitive amine oxidase is involved in vascular endothelial damage and in the process of atherosclerosis, through the formation of reactive aldehydes, hydrogen peroxide and ammonia from endogenous substrates. Recent evidence indicates that semicarbazide-sensitive amine oxidase may be identical with the vascular adhesion protein-1. In patients with diabetes mellitus and chronic heart failure the plasma activity is raised relative to the severity of the disease. The prognostic value of plasma semicarbazide-sensitive amine oxidase is not known. Methods and Results: Plasma semicarbazide-sensitive amine oxidase activity was measured at baseline in patients with moderate to severe chronic heart failure who participated in a large European study (PRIME-II). The 372 patients who took part in a pre-defined substudy in The Netherlands were investigated and a survival follow-up (maximum 5.4 years, mean 3.4 years) was carried out. Within the follow-up period 195 patients died. Plasma semicarbazide-sensitive amine oxidase was higher at baseline in those who died than in the survivors (653 ± 258 vs 540 ± 242 mU . 1-1, P<0.001). Dividing the patients into two groups according to plasma values above or below the median value of 550 mU . 1-1, semicarbazide-sensitive amine oxidase was found to be a prognostic parameter for survival, both in univariate (P<0.0001) and in multivariate (P=0.0106) analysis. Semicarbazide-sensitive amine oxidase values >550 mU . 1-1 had a 1.50 (95% CI, 1.10.-2.04) times increased risk of death. Conclusion: The finding that plasma semicarbazide-sensitive amine oxidase is an independent prognostic marker for mortality in chronic heart failure supports the concept that an elevated plasma semicarbazide-sensitive amine oxidase level has deleterious effects, possibly due to vascular endothelial damage. (C) 2000 The European Society of Cardiology.},
   author = {F. Boomsma and P. J. De Kam and G. Tjeerdsma and A. H. Van Den Meiracker and D. J. Van Veldhuisen},
   doi = {10.1053/EUHJ.2000.2176},
   issn = {0195668X},
   issue = {22},
   journal = {European Heart Journal},
   keywords = {Adhesion protein,Endothelial dysfunction,Heart failure,Prognosis,Semicarbazide-sensitive amine oxidase},
   pages = {1859-1863},
   pmid = {11052858},
   publisher = {W.B. Saunders Ltd},
   title = {Plasma semicarbazide-sensitive amine oxidase (SSAO) is an independent prognostic marker for mortality in chronic heart failure},
   volume = {21},
   year = {2000},
}
@article{Andrés2001,
   abstract = {Semicarbazide-sensitive amine oxidase (SSAO), widely distributed in highly vascularized mammalian tissues, metabolizes endogenous and xenobiotic aromatic and aliphatic monoamines. To assess whether its physiological role in humans is restricted to oxidation, we used an immunohistochemical approach to examine the cellular localization of SSAO in human peripheral tissues (adrenal gland, duodenum, heart, kidney, lung, liver, pancreas, spleen, thyroid gland, and blood vessels) and also analyzed its subcellular localization. The results are in agreement with the specific activities also determined in the same samples and are discussed with reference to the tissue distribution of monoamine oxidase A and B. Together with the oxidative deamination of monoamines, SSAO cellular localization indicates that, in most human peripheral tissues, it might participate in the regulation of physiological processes via H2O2 generation.},
   author = {N. Andrés and J. M. Lizcano and M. J. Rodríguez and M. Romera and M. Unzeta and N. Mahy},
   doi = {10.1177/002215540104900208},
   issn = {0022-1554},
   issue = {2},
   journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society},
   keywords = {Amine Oxidase (Copper-Containing) / antagonists & inhibitors,Amine Oxidase (Copper-Containing) / metabolism*,Cell Line,Enzyme Inhibitors / pharmacology*,Humans,Immunoblotting,Immunohistochemistry,J M Lizcano,MEDLINE,N Andrés,N Mahy,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,Organ Specificity,PubMed Abstract,Research Support,Semicarbazides / pharmacology*,doi:10.1177/002215540104900208,pmid:11156689},
   pages = {209-217},
   pmid = {11156689},
   publisher = {J Histochem Cytochem},
   title = {Tissue activity and cellular localization of human semicarbazide-sensitive amine oxidase},
   volume = {49},
   url = {https://pubmed.ncbi.nlm.nih.gov/11156689/},
   year = {2001},
}
@article{Kinemuchi2004,
   abstract = {Semicarbazide-sensitive amine oxidase (SSAO, EC 1.4.3.6) is a group of enzymes highly sensitive to inhibition by semicarbazide. This high sensitivity distinguishes these enzymes from monoamine oxidase (MAO). Various mammalian tissues contain membrane-bound SSAO which metabolizes only the primary monoamines. Vascular and non-vascular smooth muscle cells have particularly high SSAO activity, but recently the enzyme activity has also been found in non-vascular smooth muscle cells. The substrate specificity of SSAO shows considerable species-related variations. A variety of compounds inhibiting MAO activity has also been identified as SSAO inhibitors. Among inhibitors, there is no specific SSAO inhibitor so far tested. Many studies reinforce the conclusion that inhibitory properties of some compounds against MAO activities has been markedly differed from their properties as SSAO inhibitors. 2-Bromoethylamine has been recently developed with a potent, selective and suicide SSAO inhibitor without any inhibitory effect on MAO activity Using this inhibitor, it is possible to study the role of the enzyme in mammalian tissues. As physiological role the increased concentrations of SSAO, especially in blood plasma, have been found in diabetic patients and experimental animals. This enzyme was found to be associated with translocation of the glucose transporter GLUT4 into the adipose cell surface and involved in the signaling of glucose uptake. Recent studies showed that vascular SSAO metabolizes endogenous primary amines, allylamine, methylamine and aminoacetone, to the corresponding cytotoxic aldehydes. These aldehydes have been linked to the ability of diabetic complications such as neuropathy, retinopathy and nephropathy. Overproduction of such toxic aldehydes produced by increased SSAO activity was proposed to be potentially hazardous in diabetic complications. Thus, reduction of inhibition of SSAO may be beneficial in these pathological conditions. Clearly species-related differences in properties of SSAO must be taken into account in this respect, particularly when assessing if SSAO inhibition may have great application in human. © 2003 Elsevier Inc. All rights reserved.},
   author = {Hiroyasu Kinemuchi and Haruyo Sugimoto and Toshio Obata and Nobunori Satoh and Shiro Ueda},
   doi = {10.1016/S0161-813X(03)00118-9},
   issn = {0161813X},
   issue = {1-2},
   journal = {NeuroToxicology},
   keywords = {2-Bromoethylamine,Diabetic complication,Diabetis,SSAO inhibitor,Semicarbazide-sensitive amine oxidase (SSAO),Toxic aldehyde},
   pages = {325-335},
   pmid = {14697907},
   publisher = {Elsevier},
   title = {Selective Inhibitors of Membrane-Bound Semicarbazide-Sensitive Amine Oxidase (SSAO) Activity in Mammalian Tissues},
   volume = {25},
   year = {2004},
}
@article{Stolen2004,
   abstract = {Semicarbazide-sensitive amine oxidases (SSAO) are enzymes that are capable of deaminating primary amine to produce aldehyde, ammonia, and hydrogen peroxide. This activity has been associated with vascular adhesion protein-1 (VAP-1) and is found in the serum, endothelium, adipose, and smooth muscle of mammals. Circulating SSAC activity is increased in congestive heart failure, diabetes, and inflammatory liver diseases. To investigate the origin of circulating SSAO activity, two transgenic mouse models were created with full-length human VAP-1 (hVAP-1) expressed on either endothelial (mTIEhVAP-1) or adipose tissues (aP2hVAP-1), with tie-1 and adipocyte P2 promoters, respectively. Under normal conditions a circulating form of hVAP-1 was found at high levels in the serum of mice with endothelium-specific expression and at low levels in the serum of mice with adipose specific expression. The level of circulating hVAP-1 in the transgenic mice varied with gender, transgene zygosity, diabetes, and fasting. Serum SSAO activity was absent from VAP-1 knockout mice and endothelial cell-specific expression of human VAP-1 restored SSAO activity to the serum of VAP-1 knockout mice. Together, these experiments show that in the mouse VAP-1 is the only source of serum SSAO, that under physiological conditions vascular endothelial cells can be a major source of circulating VAP-1 protein and SSAO, and that serum VAP-1 can originate from both endothelial cells and adipocytes during experimental diabetes. An increased endothelial cell capacity for lymphocyte binding and altered expression of redox-sensitive proteins was also associated with the mTIEhVAP-1 transgene.},
   author = {Craig M. Stolen and Gennady G. Yegutkin and Riikka Kurkijärvi and Petri Bono and Kari Alitalo and Sirpa Jalkanen},
   doi = {10.1161/01.RES.0000134630.68877.2F},
   issn = {00097330},
   issue = {1},
   journal = {Circulation Research},
   keywords = {Diabetes,Hydrogen peroxide,Transgenic mice,Vascular disease,Vascular endothelium},
   month = {7},
   pages = {50-57},
   pmid = {15178639},
   title = {Origins of serum semicarbazide-sensitive amine oxidase},
   volume = {95},
   year = {2004},
}
@article{Obata2006,
   abstract = {The enzyme of semicarbazide-sensitive amine oxidase (SSAO) activity has been reported to be elevated in blood from diabetic patients. SSAO are widely distributed in plasma membranes of various tissues and blood plasma. SSAO-mediated production of toxic aldehydes has been proposed to be related to pathophysiological conditions. Cytotoxic metabolites by SSAO may cause endothelial injury and subsequently induce atherosclerosis. The precise physiological functions of SSAO could play an important role in the control of energy balance in adipose tissue. It is possible that the increased SSAO activity in diabetes may be a result of up-regulation due to increase of SSAO substrates, such as methylamine or aminoacetone. SSAO could play an important role in the regulation of adipocyte homeostasis. Inhibition of SSAO could be of therapeutic value for treatment of diabetic patient. © 2006 Elsevier Inc. All rights reserved.},
   author = {Toshio Obata},
   doi = {10.1016/j.lfs.2006.01.017},
   issn = {00243205},
   issue = {5},
   journal = {Life Sciences},
   keywords = {Atherosclerosis,Cytotoxic aldehyde,Diabetes,Methylamine,Semicarbazide-sensitive amine oxidase (SSAO)},
   month = {6},
   pages = {417-422},
   pmid = {16487546},
   title = {Diabetes and semicarbazide-sensitive amine oxidase (SSAO) activity: A review},
   volume = {79},
   year = {2006},
}
@article{Visentin2005,
   abstract = {A soluble form of semicarbazide-sensitive amine oxidase (SSAO) circulating in plasma is known to increase in type 1 and 2 diabetes. This cuproenzyme generates hydrogen peroxide, ammonia, and aldehydes when oxidizing circulating biogenic or exogenous amines. Based on the angiotoxicity of these products, inhibition of SSAO has been proposed to prevent vascular complications of diabetes. However, substrates of SSAO and monoamine oxidase (MAO) have been recently evidenced to activate glucose utilisation in insulin-sensitive tissues and to exhibit antihyperglycemic actions. To determine whether amine oxidase blockade or activation could be beneficial for diabetes, we aimed at comparing the influence of prolonged treatments with semicarbazide (SSAO-inhibitor), pargyline (MAO-inhibitor), or tyramine (amine oxidase substrate) on amine oxidase activities and glycemic control in streptozotocin-induced diabetic rats. The increase in plasma SSAO was confirmed in diabetic rats, while MAO and SSAO were decreased in subcutaneous adipose tissue when compared with normoglycemic controls. Among the diabetic rats, only those receiving tyramine exhibited slightly decreased hyperglycemia and improved glucose tolerance. Adipocytes from untreated or treated diabetic rats shared similar sensitivity to insulin. However glucose uptake activation and lipolysis inhibition in response to amine oxidase substrates combined with vanadate were impaired in rats treated with amine oxidase inhibitors. Thus, amine oxidase inhibition does not improve metabolic control while prolonged administration of tyramine slightly improves glucose disposal. It is therefore concluded that amine oxidase activation by increased substrate supply elicits insulin-like actions that may be more beneficial in diabetes than SSAO inhibition formerly proposed to prevent vascular complications. © 2005 Elsevier B.V. All rights reserved.},
   author = {Virgile Visentin and Sandy Bour and Jérémie Boucher and Danielle Prévot and Philippe Valet and Catherine Ordener and Angelo Parini and Christian Carpéné},
   doi = {10.1016/j.ejphar.2005.08.051},
   issn = {00142999},
   issue = {1-3},
   journal = {European Journal of Pharmacology},
   keywords = {Adipose tissue,Diabetes,Insulin,Monoamine oxidase,SSAO (Semicarbazide-sensitive amine oxidase)},
   month = {10},
   pages = {139-146},
   pmid = {16202994},
   title = {Glucose handling in streptozotocin-induced diabetic rats is improved by tyramine but not by the amine oxidase inhibitor semicarbazide},
   volume = {522},
   year = {2005},
}

@article{Beisswenger2005,
   abstract = {Dicarbonyl and oxidative stress may play important roles in the development of diabetes complications, and their response to hyperglycemia could determine individual susceptibility to diabetic nephropathy. This study examines the relationship of methylglyoxal, 3-deoxyglucosone (3DG), and oxidative stress levels to diabetic nephropathy risk in three populations with diabetes. All subjects in the Overt Nephropathy Progressor/Nonprogressor (ONPN) cohort (n = 14), the Natural History of Diabetic Nephropathy study (NHS) cohort (n = 110), and the Pima Indian cohort (n = 45) were evaluated for clinical nephropathy, while renal structural measures of fractional mesangial volume [Vv(Mes/glom)] and glomerular basement membrane (GBM) width were determined by electron microscopy morphometry in the NHS and Pima Indian cohorts. Methylglyoxal and 3DG levels reflected dicarbonyl stress, while reduced glutathione (GSH) and urine 8-isoprostane (8-IP) measured oxidative stress. Cross-sectional measures of methylglyoxal production by red blood cells incubated in 30 mmol/l glucose were increased in nephropathy progressors relative to nonprogressors in the ONPN (P = 0.027) and also reflected 5-year GBM thickening in the NHS cohort (P = 0.04). As nephropathy progressed in the NHS cohort, in vivo levels of methylglyoxal (P = 0.036), 3DG (P = 0.004), and oxidative stress (8-IP, P = 0.007 and GSH, P = 0.005) were seen, while increased methylglyoxal levels occurred as nephropathy progressed (P = 0.0016) in the type 2 Pima Indian cohort. Decreased glyceraldehyde-3-phosphate dehydrogenase activity also correlated with increased methylglyoxal levels (P = 0.003) in the NHS cohort. In conclusion, progression of diabetic nephropathy is significantly related to elevated dicarbonyl stress and possibly related to oxidative stress in three separate populations, suggesting that these factors play a role in determining individual susceptibility. © 2005 by the American Diabetes Association.},
   author = {Paul J. Beisswenger and Keith S. Drummond and Robert G. Nelson and Scott K. Howell and Benjamin S. Szwergold and Michael Mauer},
   doi = {10.2337/DIABETES.54.11.3274},
   issn = {0012-1797},
   issue = {11},
   journal = {Diabetes},
   keywords = {Adolescent,Adult,Cohort Studies,Deoxyglucose / analogs & derivatives*,Deoxyglucose / metabolism,Diabetes Mellitus,Diabetic Nephropathies / complications*,Diabetic Nephropathies / metabolism*,Disease Susceptibility*,Extramural,Glycated Hemoglobin,Humans,Indians,Keith S Drummond,MEDLINE,Michael Mauer,N.I.H.,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,North American,Oxidative Stress*,Paul J Beisswenger,PubMed Abstract,Pyruvaldehyde / metabolism*,Research Support,Risk Factors,Type 2 / complications*,Type 2 / metabolism,doi:10.2337/diabetes.54.11.3274,pmid:16249455},
   month = {11},
   pages = {3274-3281},
   pmid = {16249455},
   publisher = {Diabetes},
   title = {Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress},
   volume = {54},
   url = {https://pubmed.ncbi.nlm.nih.gov/16249455/},
   year = {2005},
}
@article{Alouffi2019,
   abstract = {It has been well established that advanced glycation end-products (AGEs) have a strong correlation with diabetes and its secondary complications. Moreover, dicarbonyls, especially, methyl-glyoxal (MG) and glyoxal, accelerate AGEs formation and hence, have potential roles in the patho-genesis of diabetes. They can also induce oxidative stress and concomitantly decrease the efficiency of antioxidant enzymes. Increased proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta) are secreted by monocytes due to the dicarbonyl-modified proteins. High levels of blood dicarbon-yls have been identified in diabetes and its associated complications (retinopathy, nephropathy and neuropathy). This review aims to provide a better understanding by including in-depth information about the formation of MG and glyoxal through multiple pathways with a focus on their biological functions and detoxifications. The potential role of these dicarbonyls in secondary diabetic complications is also discussed.Copyright © 2020 Bentham Science Publishers.},
   author = {Sultan Alouffi and Mohd Wajid Ali Khan},
   doi = {10.2174/1389203720666191010155145},
   issn = {13892037},
   issue = {9},
   journal = {Current Protein & Peptide Science},
   month = {10},
   pages = {890-898},
   pmid = {31660813},
   publisher = {Bentham Science Publishers Ltd.},
   title = {Dicarbonyls Generation, Toxicities, Detoxifications and Potential Roles in Diabetes Complications},
   volume = {21},
   year = {2019},
}
@article{Schilter2015,
   abstract = {Background and purpose: The persistent influx of neutrophils into the lung and subsequent tissue damage are characteristics of COPD, cystic fibrosis and acute lung inflammation. VAP-1/SSAO is an endothelial bound adhesion molecule with amine oxidase activity that is reported to be involved in neutrophil egress from the microvasculature during inflammation. This study explored the role of VAP-1/SSAO in neutrophilic lung mediated diseases and examined the therapeutic potential of the selective inhibitor PXS-4728A. Methods: Mice treated with PXS-4728A underwent intra-vital microscopy visualization of the cremaster muscle upon CXCL1/KC stimulation. LPS inflammation, Klebsiella pneumoniae infection, cecal ligation and puncture as well as rhinovirus exacerbated asthma models were also assessed using PXS-4728A. Results: Selective VAP-1/SSAO inhibition by PXS-4728A diminished leukocyte rolling and adherence induced by CXCL1/KC. Inhibition of VAP-1/SSAO also dampened the migration of neutrophils to the lungs in response to LPS, Klebsiella pneumoniae lung infection and CLP induced sepsis; whilst still allowing for normal neutrophil defense function, resulting in increased survival. The functional effects of this inhibition were demonstrated in the RV exacerbated asthma model, with a reduction in cellular infiltrate correlating with a reduction in airways hyperractivity. Conclusions and implications: This study demonstrates that the endothelial cell ligand VAP-1/SSAO contributes to the migration of neutrophils during acute lung inflammation, pulmonary infection and airway hyperractivity. These results highlight the potential of inhibiting of VAP-1/SSAO enzymatic function, by PXS-4728A, as a novel therapeutic approach in lung diseases that are characterized by neutrophilic pattern of inflammation.},
   author = {Heidi C. Schilter and Adam Collison and Remo C. Russo and Jonathan S. Foot and Tin T. Yow and Angelica T. Vieira and Livia D. Tavares and Joerg Mattes and Mauro M. Teixeira and Wolfgang Jarolimek},
   doi = {10.1186/S12931-015-0200-Z},
   issn = {1465-993X},
   issue = {1},
   journal = {Respiratory research},
   keywords = {Adam Collison,Allylamine / analogs & derivatives*,Allylamine / pharmacokinetics,Allylamine / pharmacology,Amine Oxidase (Copper-Containing) / antagonists & inhibitors*,Amine Oxidase (Copper-Containing) / metabolism,Animal,Animals,Anti-Inflammatory Agents / pharmacokinetics,Anti-Inflammatory Agents / pharmacology*,Asthma / drug therapy*,Asthma / enzymology,Asthma / immunology,Asthma / physiopathology,Asthma / virology,Benzamides / pharmacokinetics,Benzamides / pharmacology*,Bronchoconstriction / drug effects,Cecum / microbiology,Cecum / surgery,Cell Adhesion Molecules / antagonists & inhibitors*,Cell Adhesion Molecules / metabolism,Disease Models,Dose-Response Relationship,Drug,Endothelial Cells / drug effects,Endothelial Cells / enzymology,Endothelial Cells / immunology,Enzyme Inhibitors / pharmacokinetics,Enzyme Inhibitors / pharmacology*,Heidi C Schilter,Inbred BALB C,Inbred C57BL,Klebsiella Infections / drug therapy*,Klebsiella Infections / enzymology,Klebsiella Infections / immunology,Klebsiella Infections / microbiology,Klebsiella pneumoniae / pathogenicity,Leukocyte Rolling / drug effects,Ligation,Lipopolysaccharides,Lung / drug effects*,Lung / enzymology,Lung / immunology,Lung / physiopathology,MEDLINE,Mice,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Neutrophil Infiltration / drug effects*,PMC4389443,Picornaviridae Infections / drug therapy*,Picornaviridae Infections / enzymology,Picornaviridae Infections / immunology,Picornaviridae Infections / physiopathology,Picornaviridae Infections / virology,Pneumonia / drug therapy*,Pneumonia / enzymology,Pneumonia / etiology,Pneumonia / immunology,PubMed Abstract,Punctures,Rats,Respiratory Tract Infections / drug therapy*,Respiratory Tract Infections / enzymology,Respiratory Tract Infections / etiology,Respiratory Tract Infections / immunology,Rhinovirus / pathogenicity,Wistar,Wolfgang Jarolimek,doi:10.1186/s12931-015-0200-z,pmid:25889951},
   month = {3},
   pmid = {25889951},
   publisher = {Respir Res},
   title = {Effects of an anti-inflammatory VAP-1/SSAO inhibitor, PXS-4728A, on pulmonary neutrophil migration},
   volume = {16},
   url = {https://pubmed.ncbi.nlm.nih.gov/25889951/},
   year = {2015},
}
@article{Jarnicki2016,
   abstract = {Background and Purpose: Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death, often induced by cigarette smoking (CS). It is characterized by pulmonary inflammation and fibrosis that impairs lung function. Existing treatments aim to control symptoms but have low efficacy, and there are no broadly effective treatments. A new potential target is the ectoenzyme, semicarbazide-sensitive mono-amine oxidase (SSAO; also known as vascular adhesion protein-1). SSAO is elevated in smokers’ serum and is a pro-inflammatory enzyme facilitating adhesion and transmigration of leukocytes from the vasculature to sites of inflammation. Experimental Approach: PXS-4728A was developed as a low MW inhibitor of SSAO. A model of COPD induced by CS in mice reproduces key aspects of human COPD, including chronic airway inflammation, fibrosis and impaired lung function. This model was used to assess suppression of SSAO activity and amelioration of inflammation and other characteristic features of COPD. Key Results: Treatment with PXS-4728A completely inhibited lung and systemic SSAO activity induced by acute and chronic CS-exposure. Daily oral treatment inhibited airway inflammation (immune cell influx and inflammatory factors) induced by acute CS-exposure. Therapeutic treatment during chronic CS-exposure, when the key features of experimental COPD develop and progress, substantially suppressed inflammatory cell influx and fibrosis in the airways and improved lung function. Conclusions and Implications: Treatment with a low MW inhibitor of SSAO, PXS-4728A, suppressed airway inflammation and fibrosis and improved lung function in experimental COPD, demonstrating the therapeutic potential of PXS-4728A for this debilitating disease.},
   author = {A. G. Jarnicki and H. Schilter and G. Liu and K. Wheeldon and A. T. Essilfie and J. S. Foot and T. T. Yow and W. Jarolimek and Philip M. Hansbro},
   doi = {10.1111/bph.13573},
   issn = {14765381},
   issue = {22},
   journal = {British Journal of Pharmacology},
   pages = {3161-3175},
   pmid = {27495192},
   publisher = {John Wiley and Sons Inc.},
   title = {The inhibitor of semicarbazide-sensitive amine oxidase, PXS-4728A, ameliorates key features of chronic obstructive pulmonary disease in a mouse model},
   volume = {173},
   year = {2016},
}
@article{Tábi2013,
   abstract = {SSAO/VAP-1 participates in the accumulation of leukocytes at the site of inflammation. A new SSAO inhibitor, SzV-1287 was demonstrated to inhibit both acute and chronic inflammation in rats more effectively than the known enzyme inhibitor, LJP-1207. Surprisingly, the SSAO activity was not increased, but decreased both in acute and chronic inflammation. Though experiments are in progress to clarify these findings, the enzyme might play a role in the very early phase of inflammation and be inactivated during leukocyte extravasation. © 2012 Springer-Verlag Wien.},
   author = {Tamás Tábi and Éva Szöko and Anita Mérey and Veronika Tóth and Péter Mátyus and Klára Gyires},
   doi = {10.1007/S00702-012-0961-1},
   issn = {1435-1463},
   issue = {6},
   journal = {Journal of neural transmission (Vienna, Austria : 1996)},
   keywords = {Amine Oxidase (Copper-Containing) / metabolism*,Animal,Animals,Arthritis,Carrageenan / toxicity,Disease Models,Enzyme Inhibitors / therapeutic use*,Enzymologic / drug effects,Eva Szökő,Experimental / chemically induced,Experimental / drug therapy*,Functional Laterality,Gene Expression Regulation,Hydrazines / therapeutic use,Inflammation / chemically induced,Inflammation / drug therapy*,Inflammation / ethnology*,Klára Gyires,MEDLINE,Male,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,Oxazoles / therapeutic use*,Oximes / therapeutic use*,PubMed Abstract,Rats,Research Support,Tamás Tábi,Time Factors,Wistar,doi:10.1007/s00702-012-0961-1,pmid:23263543},
   month = {6},
   pages = {963-967},
   pmid = {23263543},
   publisher = {J Neural Transm (Vienna)},
   title = {Study on SSAO enzyme activity and anti-inflammatory effect of SSAO inhibitors in animal model of inflammation},
   volume = {120},
   url = {https://pubmed.ncbi.nlm.nih.gov/23263543/},
   year = {2013},
}
@article{Hernandez2006,
   abstract = {Semicarbazide sensitive amine oxidase (SSAO) metabolizes oxidative deamination of primary aromatic and aliphatic amines. It is selectively expressed in vascular cells of blood vessels, but it is also circulating in blood plasma. SSAO activity in plasma is increased in some diseases associated with vascular complications and its catalytic products may cause tissue damage. We examined the effect of the oxidation of the SSAO substrate, methylamine, on cultured smooth muscle cells. Cell incubation with methylamine plus soluble SSAO, contained in bovine serum, resulted toxic to rat aorta A7r5 and human aortic smooth muscle cells, as measured by MTT reduction. This effect was completely reverted by specific SSAO inhibitors, indicating that the toxicity was mediated by the end products generated. Moreover, SSAO-mediated deamination of methylamine induced apoptosis in A7r5 cells, detected by chromatin condensation, Caspase-3 activation, PARP cleavage and cytochrome c release to cytosol. Formaldehyde, rather than H2O2, resulted to be a strong apoptotic inducer to A7r5 cells. Taken together, the results suggest that increased plasma SSAO activity in pathological conditions, could contribute to apoptosis in smooth muscle cells, leading to vascular tissue damage. © 2006 Elsevier B.V. All rights reserved.},
   author = {Mar Hernandez and Montse Solé and Mercè Boada and Mercedes Unzeta},
   doi = {10.1016/J.BBAMCR.2005.11.017},
   issn = {0167-4889},
   issue = {2},
   journal = {Biochimica et Biophysica Acta (BBA) - Molecular Cell Research},
   keywords = {Aortic smooth muscle cell,Apoptosis,Formaldehyde,Hydrogen peroxide,Methylamine,Semicarbazide Sensitive Amine Oxidase},
   month = {2},
   pages = {164-173},
   pmid = {16448709},
   publisher = {Elsevier},
   title = {Soluble Semicarbazide Sensitive Amine Oxidase (SSAO) catalysis induces apoptosis in vascular smooth muscle cells},
   volume = {1763},
   year = {2006},
}
@article{Yu1998,
   abstract = {The mouse is known to be highly resistant to atherosclerosis. However, some inbred mouse strains are vulnerable to atherosclerosis when they are fed a high-cholesterol, high-fat diet. Increased deamination of methylamine (MA) and the subsequent production of formaldehyde has been recently shown to be a potential risk factor of atherosclerosis. In the present study semicarbazide- sensitive amine oxidase (SSAO)-mediated MA turnover in C57BL/6 mouse, a strain very susceptible to atherosclerosis, has been assessed in comparison to a moderate, i.e. BALB/c, and resistant, i.e. CD1, mouse strains. Kidney and aorta SSAO activities were found to be significantly increased in C57BL/6 in comparison to BALB/c and CD 1 mice. A significant increase of urinary MA and formaldehyde were detected in C57BL/6. [14C]MA following intravenous injection would be quickly metabolized by SSAO. The labeled formaldehyde product would cross link with proteins. C57BL/6 exhibits significantly higher labeled protein adducts than BALB/c and CD1 in response to [14C]MA. The results indicated that mice vulnerable to atherosclerosis possess an increased SSAO-mediated MA turnover. The increase of production of formaldehyde, possibly other aldehydes, may induce endothelial injury or be chronically involved in protein cross-linking and subsequent angiopathy.},
   author = {P. H. Yu and Y. L. Deng},
   doi = {10.1016/S0021-9150(98)00142-7},
   issn = {0021-9150},
   issue = {2},
   journal = {Atherosclerosis},
   keywords = {Acetaldehyde,Amine oxidase,Formaldehyde,Methylamine,Methylglyoxal,SSAO},
   month = {10},
   pages = {357-363},
   pmid = {9862279},
   publisher = {Elsevier},
   title = {Endogenous formaldehyde as a potential factor of vulnerability of atherosclerosis: involvement of semicarbazide-sensitive amine oxidase-mediated methylamine turnover},
   volume = {140},
   year = {1998},
}
@article{Iglesias-Osma2005,
   abstract = {It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.},
   author = {Maria Carmen Iglesias-Osma and Sandy Bour and Maria Jose Garcia-Barrado and Virgile Visentin and Maria Francisca Pastor and Xavier Testar and Luc Marti and Gemma Enrique-Tarancon and Philippe Valet and Julio Moratinos and Christian Carpéné},
   doi = {10.1016/J.PHRS.2005.07.008},
   issn = {1043-6618},
   issue = {6},
   journal = {Pharmacological Research},
   keywords = {Glucose homeostasis,Insulin-like activity,Lipolysis,Semicarbazide-sensitive amine oxidase},
   month = {12},
   pages = {475-484},
   pmid = {16135411},
   publisher = {Academic Press},
   title = {Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism},
   volume = {52},
   year = {2005},
}
@article{Manasieva2022,
   abstract = {Vascular smooth muscle cells (VSMCs) are the main stromal cells in the medial layer of the vascular wall. These cells produce the extracellular matrix (ECM) and are involved in many pathological changes in the vascular wall. Semicarbazide-sensitive amine oxidase (SSAO) and lysyl oxidase (LOX) are vascular enzymes associated with the development of atherosclerosis. In the vascular smooth muscle cells, increased SSAO activity elevates reactive oxygen species (ROS) and induces VSMCs death; increased LOX induces chemotaxis through hydrogen peroxide dependent mechanisms; and decreased LOX contributes to endothelial dysfunction. This study investigates the relationship between SSAO and LOX in VSMCs by studying their activity, protein, and mRNA levels during VSMCs passaging and after silencing the LOX gene, while using their respective substrates and inhibitors. At the basal level, LOX activity decreased with passage and its protein expression was maintained between passages. βAPN abolished LOX activity (** p < 0.01 for 8 vs. 3 and * p < 0.05 for 5 vs. 8) and had no effect on LOX protein and mRNA levels. MDL72527 reduced LOX activity at passage 3 and 5 (## p < 0.01) and had no effect on LOX protein, and mRNA expression. At the basal level, SSAO activity also decreased with passage, and its protein expression was maintained between passages. MDL72527 abolished SSAO activity (**** p < 0.0001 for 8 vs. 3 and * p < 0.05 for 5 vs. 8), VAP-1 expression at passage 5 (** p < 0.01) and 8 (**** p < 0.0001), and Aoc3 mRNA levels at passage 8 (* p < 0.05). βAPN inhibited SSAO activity (**** p < 0.0001 for 5 vs. 3 and 8 vs. 3 and * p < 0.05 for 5 vs. 8), VAP-1 expression at passage 3 (* p < 0.05), and Aoc3 mRNA levels at passage 3 (* p < 0.05). Knockdown of the LOX gene (**** p < 0.0001 for Si6 vs. Sictrl and *** p < 0.001 for Si8 vs. Sictrl) and LOX protein (** p < 0.01 for Si6 and Si8 vs. Sictrl) in VSMCs at passage 3 resulted in a reduction in Aoc3 mRNA (#### p < 0.0001 for Si6 vs. Sictrl and ### p < 0.001 for Si8 vs. Sictrl) and VAP-1 protein (# p < 0.05 for Si8 vs. Sictrl). These novel findings demonstrate a passage dependent decrease in LOX activity and increase in SSAO activity in rat aortic VSMCs and show an association between both enzymes in early passage rat aortic VSMCs, where LOX was identified as a regulator of SSAO activity, protein, and mRNA expression.},
   author = {Vesna Manasieva and Shori Thakur and Lisa A. Lione and Jessal Patel and Anwar Baydoun and John Skamarauskas},
   doi = {10.3390/BIOM12111563},
   issn = {2218273X},
   issue = {11},
   journal = {Biomolecules},
   keywords = {MDL72527,amine oxidase copper containing 3 (Aoc3),benzylamine,cadaverine,copper amine oxidases,lysyl oxidase (LOX),semicarbazide sensitive amine oxidase (SSAO),vascular adhesion protein (VAP-1),vascular smooth muscle cells,βAPN},
   month = {11},
   pmid = {36358914},
   publisher = {MDPI},
   title = {Semicarbazide-Sensitive Amine Oxidase (SSAO) and Lysyl Oxidase (LOX) Association in Rat Aortic Vascular Smooth Muscle Cells},
   volume = {12},
   year = {2022},
}
@article{Manasieva2023,
   abstract = {Semicarbazide-sensitive amine oxidase (SSAO) is both a soluble- and membrane-bound transmembrane protein expressed in the vascular endothelial and in smooth muscle cells. In vascular endothelial cells, SSAO contributes to the development of atherosclerosis by mediating a leukocyte adhesion cascade; however, its contributory role in the development of atherosclerosis in VSMCs has not yet been fully explored. This study investigates SSAO enzymatic activity in VSMCs using methylamine and aminoacetone as model substrates. The study also addresses the mechanism by which SSAO catalytic activity causes vascular damage, and further evaluates the contribution of SSAO in oxidative stress formation in the vascular wall. SSAO demonstrated higher affinity for aminoacetone when compared to methylamine (Km = 12.08 µM vs. 65.35 µM). Aminoacetone- and methylamine-induced VSMCs death at concentrations of 50 & 1000 µM, and their cytotoxic effect, was reversed with 100 µM of the irreversible SSAO inhibitor MDL72527, which completely abolished cell death. Cytotoxic effects were also observed after 24 h of exposure to formaldehyde, methylglyoxal and H2O2. Enhanced cytotoxicity was detected after the simultaneous addition of formaldehyde and H2O2, as well as methylglyoxal and H2O2. The highest ROS production was observed in aminoacetone- and benzylamine-treated cells. MDL72527 abolished ROS in benzylamine-, methylamine- and aminoacetone-treated cells (**** p < 0.0001), while βAPN demonstrated inhibitory potential only in benzylamine-treated cells (* p < 0.05). Treatment with benzylamine, methylamine and aminoacetone reduced the total GSH levels (**** p < 0.0001); the addition of MDL72527 and βAPN failed to reverse this effect. Overall, a cytotoxic consequence of SSAO catalytic activity was observed in cultured VSMCs where SSAO was identified as a key mediator in ROS formation. These findings could potentially associate SSAO activity with the early developing stages of atherosclerosis through oxidative stress formation and vascular damage.},
   author = {Vesna Manasieva and Shori Thakur and Lisa A. Lione and Anwar R. Baydoun and John Skamarauskas},
   doi = {10.3390/IJMS24054946},
   issn = {1422-0067},
   issue = {5},
   journal = {International Journal of Molecular Sciences 2023, Vol. 24, Page 4946},
   keywords = {aminoacetone,formaldehyde,hydrogen peroxide,methylamine,methylglyoxal,reactive oxygen species,semicarbazide,sensitive amine oxidase,vascular smooth muscle cells},
   month = {3},
   pages = {4946},
   pmid = {36902376},
   publisher = {Multidisciplinary Digital Publishing Institute},
   title = {The Impact of Semicarbazide Sensitive Amine Oxidase Activity on Rat Aortic Vascular Smooth Muscle Cells},
   volume = {24},
   url = {https://www.mdpi.com/1422-0067/24/5/4946/htm https://www.mdpi.com/1422-0067/24/5/4946},
   year = {2023},
}
@article{Li2019,
   abstract = {Background: The present study aimed to investigate the inhibitory effects of aminoguanidine (AG) and 2-bromoethylamine (2-BEA) on the semicarbazide-sensitive amine oxidase (SSAO) activity both in vitro and in vivo, and the prevention role of AG and 2-BEA in the morphology of aorta and kidney in diabetic rats. Methods: The aortic homogenates isolated from Sprague-Dawley (SD) rats were treated with different concentrations of AG or 2-BEA to investigate the inhibitory effects on the SSAO activity in vitro, using benzylamine as the substrate. In addition, 65 male SD rats were randomly assigned into normal control (NC) (n = 10), NC + AG (n = 10), NC + 2-BEA (n = 10) and diabetes mellitus (DM) model groups (n = 35). Type 1 diabetic rat model was induced by intraperitoneal injection of 1% streptozotocin-sodium citrate buffer 55 mg/kg. After establishing the diabetic rat model by a single intraperitoneal injection of streptozotocin. Except those failed in modeling, 30 rats in the DM model group were further randomly divided into the DM, DM + AG, DM + 2-BEA groups (n = 10 in each). Rats in the DM + AG and NC + AG group were intraperitoneally injected with AG (25 mg/kg),those in the DM + 2-BEA and NC + 2-BEA group were administered with 2-BEA (20 mg/kg) daily for eight weeks. After eight weeks of treatment, the SSAO activity in the plasma and aorta, and plasma levels of formaldehyde (FA) and methylamine (MA) were measured by high performance liquid chromatograph. Radioimmunoassay was used to determine the plasma endothelin-1 (ET-1) concentration, while nitric acid deoxidized enzyme method was performed to detect the plasma nitrate/nitrite (NO(x)-) level. Besides, the morphological changes of aorta and kidney tissues were examined by optical and electron microscopes. Results: Both AG and 2-BEA exerted strong inhibitory effect on the aortic SSAO activity in vitro, with the IC50 values of 12.76 μmol/L and 3.83 μmol/L, respectively. Compared with the NC group, the SSAO activity in the plasma and aorta, and plasma levels of MA and ET-1 were significantly increased (P < 0.01), whereas the plasma NO(x)- level was obviously lower in the DM group (P < 0.01). A significantly decreased SSAO activity and plasma ET-1 level, as well as obviously increased plasma levels of MA and NO(x)- were observed in the DM + AG and DM + 2-BEA groups in comparison with the DM group (P < 0.01). However, there was no significant difference in plasma FA concentration among all the groups. Besides, the morphological changes of aorta and kidney were apparently alleviated in the DM + AG and DM + 2-BEA groups as compared with the DM group. Conclusions: Both AG and 2-BEA can inhibit the SSAO activity in the plasma and aorta. Moreover, the inhibitory effects of AG and 2-BEA on the SSAO-mediated oxidative deamination had great benefit in the morphological changes of aorta and kidney in diabetic rats.},
   author = {Chaosheng Li and Zhenhua Wang and Xiaoli Li and Jun Chen},
   doi = {10.1186/S12902-019-0392-1},
   issn = {1472-6823},
   issue = {1},
   journal = {BMC endocrine disorders},
   keywords = {Amine Oxidase (Copper-Containing) / antagonists & inhibitors*,Animals,Aorta / cytology*,Aorta / drug effects,Aorta / enzymology,Chaosheng Li,Diabetes Mellitus,Enzyme Inhibitors / pharmacology,Ethylamines / pharmacology*,Experimental / drug therapy,Experimental / enzymology,Experimental / pathology*,Guanidines / pharmacology*,Jun Chen,Kidney / cytology*,Kidney / drug effects,Kidney / enzymology,MEDLINE,Male,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PMC6558804,Protective Agents / pharmacology*,PubMed Abstract,Rats,Sprague-Dawley,Zhenhua Wang,doi:10.1186/s12902-019-0392-1,pmid:31182088},
   month = {6},
   pmid = {31182088},
   publisher = {BMC Endocr Disord},
   title = {Effects of semicarbazide-sensitive amine oxidase inhibitors on morphology of aorta and kidney in diabetic rats},
   volume = {19},
   url = {https://pubmed.ncbi.nlm.nih.gov/31182088/},
   year = {2019},
}
@article{Morin2001,
   abstract = {Semicarbazide-sensitive amine oxidases (SSAO) are widely distributed enzymes scavenging biogenic or exogenous amines and generating hydrogen peroxide. We asked whether human adipose tissue could express SSAO. Since hydrogen peroxide exhibits pharmacological insulin-like effects, we also tested whether its endogenous production by SSAO could mimic several insulin effects on adipocytes, such as stimulation of glucose uptake and inhibition of lipolysis. The benzylamine oxidation by human adipose tissue was inhibited by semicarbazide or hydralazine and resistant to pargyline or selegiline. It was due to an SSAO activity localized in adipocyte membranes. A protein of 100-kDa and a 4-kb mRNA corresponding to SSAO were identified in either mammary or abdominal subcutaneous fat depots. In isolated adipocytes, SSAO oxidized similarly benzylamine and methylamine that dose dependently stimulated glucose transport in a semicarbazide-sensitive manner. Antioxidants also inhibited the benzylamine and methylamine effects. Moreover, the ability of diverse substrates to be oxidized by adipocytes was correlated to their effect on glucose transport. Benzylamine and methylamine exerted antilipolytic effects with a maximum attained at 1 mM. These results show that human adipocytes express a membrane-bound SSAO that not only readily oxidizes exogenous amines and generates H(2)O(2), but that also interplays with glucose and lipid metabolism by exerting insulin-like actions. Based on these results and the fact that variations in plasma levels of the soluble form of SSAO have been previously reported in diabetes, we propose that determination of adipocyte SSAO, feasible on subcutaneous microbiopsies, could bring relevant information in pathologies such as obesity or diabetes.},
   author = {N Morin and J M Lizcano and E Fontana and L Marti and F Smih and P Rouet and D Prévot and A Zorzano and M Unzeta and C Carpéné},
   issn = {0022-3565},
   issue = {2},
   journal = {The Journal of pharmacology and experimental therapeutics},
   month = {5},
   pages = {563-72},
   pmid = {11303044},
   title = {Semicarbazide-sensitive amine oxidase substrates stimulate glucose transport and inhibit lipolysis in human adipocytes.},
   volume = {297},
   year = {2001},
}
@article{Sun2018,
   abstract = {Beyond cholesterol reduction, statins mediate their beneficial effects on stroke patients through pleiotropic actions. They have shown anti-inflammatory properties by a number of different mechanisms, including the inhibition of NF-κB transcriptional activity and the consequent increase and release of adhesion molecules. We have studied simvastatin's effects on the vascular enzyme semicarbazide-sensitive amine oxidase/vascular adhesion protein 1 (SSAO/VAP-1), which is involved in stroke-mediated brain injury. SSAO/VAP-1 has leukocyte-binding capacity and mediates the expression of other adhesion proteins through signaling molecules generated by its catalytic activity. Our results indicate that soluble SSAO/VAP-1 is released into the bloodstream after an ischemic stimulus, in parallel with an increase in E-selectin and VCAM-1 and correlating with infarct volume. Simvastatin blocks soluble SSAO/VAP-1 release and prevents E-selectin and VCAM-1 overexpression as well. Simvastatin also effectively blocks SSAO/VAP-1-mediated leukocyte adhesion, although it is not an enzymatic inhibitor of SSAO in vitro. In addition, simvastatin-induced changes in adhesion molecules are greater in human brain endothelial cell cultures expressing SSAO/VAP-1, compared to those not expressing it, indicating some synergic effect with SSAO/VAP-1. We think that part of the beneficial effect of simvastatin in stroke is mediated by the attenuation of the SSAO/VAP-1-dependent inflammatory response.},
   author = {Ping Sun and Mar Hernandez-Guillamón and Mireia Campos-Martorell and Alba Simats and Joan Montaner and Mercedes Unzeta and Montse Solé},
   doi = {10.1016/J.BBADIS.2017.11.014},
   issn = {0925-4439},
   issue = {2},
   journal = {Biochimica et biophysica acta. Molecular basis of disease},
   keywords = {Amine Oxidase (Copper-Containing) / metabolism*,Animal,Animals,Brain / metabolism,Brain Ischemia / drug therapy,Brain Ischemia / metabolism*,Cell Adhesion,Cell Adhesion Molecules / metabolism*,Cell Line,Disease Models,E-Selectin / metabolism,Endothelial Cells,Human Umbilical Vein Endothelial Cells,Humans,Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology,Inflammation / drug therapy,Inflammation / metabolism*,MEDLINE,Male,Mar Hernandez-Guillamón,Montse Solé,NCBI,NF-KappaB Inhibitor alpha / metabolism,NF-kappa B / metabolism,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,Ping Sun,PubMed Abstract,Rats,Research Support,Simvastatin / pharmacology*,Stroke / metabolism*,Stroke / pathology,Vascular Cell Adhesion Molecule-1 / metabolism,Wistar,doi:10.1016/j.bbadis.2017.11.014,pmid:29175057},
   month = {2},
   pages = {542-553},
   pmid = {29175057},
   publisher = {Biochim Biophys Acta Mol Basis Dis},
   title = {Simvastatin blocks soluble SSAO/VAP-1 release in experimental models of cerebral ischemia: Possible benefits for stroke-induced inflammation control},
   volume = {1864},
   url = {https://pubmed.ncbi.nlm.nih.gov/29175057/},
   year = {2018},
}
@article{Martin2019,
   abstract = {Global obesity rates have reached pandemic proportions, increasing the risk of metabolic complications for hundreds of millions of individuals worldwide. Gaining insight on adipose tissue biology and understanding how fat pads behave during obesity is critical to investigate metabolic syndromes. Elucidation of cellular signaling pathways engaged by adipose tissue both in health and disease requires standardized protocols for protein extraction that yield consistently pure samples. A recurrent problem of currently available protocols is lipid or detergent contamination in extracted protein samples, which renders protein quantification inaccurate and, as a consequence, consistency and reproducibility of protein loading become unreliable. To overcome this problem, we improved the process of adipose tissue protein extraction by improving tissue lysis and decreasing lipid contamination. Here we describe the Removal of Excess Lipids (RELi) protocol to obtain increased yields of total proteins extracted from adipose tissue. The RELi protocol allows accurate and reproducible adipose tissue sample preparation for Western blot analysis and other investigative techniques requiring adipose tissue-derived proteins.},
   author = {R. Diaz Marin and S. Crespo-Garcia and Ariel Molly Wilson and P. Sapieha},
   doi = {10.1016/J.MEX.2019.04.010},
   issn = {2215-0161},
   journal = {MethodsX},
   keywords = {Adipose tissue,BAT,Protein extraction,Removal of excess lipids (RELi) protocol for protein extraction from white, brown and beige adipose,WAT,Western blot},
   month = {1},
   pages = {918-928},
   publisher = {Elsevier},
   title = {RELi protocol: Optimization for protein extraction from white, brown and beige adipose tissues},
   volume = {6},
   year = {2019},
}
@article{Salmi1992,
   abstract = {Interactions between leukocyte surface receptors and their ligands on vascular endothelial cells control lymphocyte traffic between the blood and various lymphoid organs, as well as extravasation of leukocytes into sites of inflammation. A heretofore undescribed 90-kilodalton human endothelial cell adhesion molecule (VAP-1) defined by a monoclonal antibody 1B2 is described. The expression pattern, molecular mass, functional properties, and an amino-terminal amino acid sequence define VAP-1 as an endothelial ligand for lymphocytes. VAP-1 helps to elucidate the complex heterotypic cell interactions that direct tissue-selective lymphocyte migration in man.},
   author = {Marko Salmi and Sirpa Jalkanen},
   doi = {10.1126/SCIENCE.1529341},
   issn = {0036-8075},
   issue = {5075},
   journal = {Science (New York, N.Y.)},
   keywords = {Amine Oxidase (Copper-Containing)*,Amino Acid Sequence,Animals,Antibodies,Arthritis,Cell Adhesion / physiology*,Cell Adhesion Molecules / chemistry,Cell Adhesion Molecules / metabolism,Cell Adhesion Molecules / physiology*,Comparative Study,Humans,Inbred BALB C,Lymphocytes / physiology*,M Salmi,MEDLINE,Mice,Molecular Sequence Data,Molecular Weight,Monoclonal,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,Nucleic Acid,PubMed Abstract,Research Support,Rheumatoid / immunology,S Jalkanen,Sequence Homology,Synovial Membrane / immunology,doi:10.1126/science.1529341,pmid:1529341},
   month = {9},
   pages = {1407-1409},
   pmid = {1529341},
   publisher = {Science},
   title = {A 90-kilodalton endothelial cell molecule mediating lymphocyte binding in humans},
   volume = {257},
   url = {https://pubmed.ncbi.nlm.nih.gov/1529341/},
   year = {1992},
}
@article{Salmi2000,
   abstract = {Lymphocyte binding to vascular endothelium is a prerequisite for the movement of immune cells from the blood into lymphoid tissues and into sites of inflammation. Human vascular adhesion protein-1 (VAP-1) is an endothelial glycoprotein involved in this interaction. It also displays an enzymatic (monoamine oxidase) activity. Here we examined how recombinant human VAP-1 mediates lymphocyte binding using rotatory and flow chamber binding assays. VAP-1 cDNA transfected into an endothelial cell line, which does not bind lymphocytes, renders the cell line capable of binding lymphocytes in a shear- dependent manner. VAP-1 transfectants bound lymphocytes 5 times better than monocytes with a preference for T killer cells, and no specific granulocyte adherence was detectable. The binding is partially inhibited by anti-VAP-1 monoclonal antibodies or by blocking lymphocyte L-selectin and CD18 integrins, but not by inhibition of several other homing-associated molecules. In contrast, CD44 ligation on lymphocytes markedly upregulates their VAP-1 - dependent adhesion, suggesting that the VAP-1 counterreceptor can be activated via CD44. The transfectant model also allowed us to perform detailed structure-function analyses of VAP-1. We show that the exposed integrin-binding motif RGD or the enzymatic activity is not indispensable for VAP-1 - dependent adhesion. Together, these data show that VAP-1 can reconstitute the lymphocyte-endothelial adhesion cascade under shear and propose a critical role for VAP-1 in lymphocyte emigration from the blood.},
   author = {Marko Salmi and Sami Tohka and Sirpa Jalkanen},
   doi = {10.1161/01.RES.86.12.1245},
   issn = {00097330},
   issue = {12},
   journal = {Circulation Research},
   keywords = {Adhesion,Cell trafficking,Enzymatic activity,Leukocyte-endothelial cell interactions,Recruitment},
   month = {6},
   pages = {1245-1251},
   pmid = {10864915},
   publisher = {Lippincott Williams and Wilkins},
   title = {Human vascular adhesion protein-1 (VAP-1) plays a critical role in lymphocyte-endothelial cell adhesion cascade under shear},
   volume = {86},
   year = {2000},
}
@article{Salmi1996,
   abstract = {The regulated interactions of leukocytes with vascular endothelial cells are crucial in controlling leukocyte traffic between blood and tissues. Vascular adhesion protein-1 (VAP-1) is a novel, human endothelial cell molecule that mediates tissue-selective lymphocyte binding. Two species (90 and 170 kD) of VAP-1 exist in lymphoid tissues. Glycosidase digestions revealed that the mature 170-kD form of VAP-1 expressed on the lumenal surfaces of vessels is a heavily sialylated glycoprotein. The sialic acids are indispensable for the function of VAP-1, since the desialylated form of VAP-1 no longer mediates lymphocyte binding. We also show that L-selectin is not required for binding of activated lymphocytes to VAP-1 under conditions of shear stress. The 90-kD form of VAP-1 was only seen in an organ culture model, and may represent a monomeric or proteolytic form of the larger species. These data indicate that L-selectin negative lymphocytes can bind to tonsillar venules via the VAP-1-mediated pathway. Moreover, our findings extend the role of carbohydrate-mediated binding in lymphocyte-endothelial cell interactions beyond the known selectins. In conclusion, VAP-1 naturally exists as a 170-kD sialoglycoprotein that uses sialic acid residues to interact with its counter-receptors on lymphocytes under nonstatic conditions.},
   author = {Marko Salmi and Sirpa Jalkanen},
   doi = {10.1084/jem.183.2.569},
   issn = {00221007},
   issue = {2},
   journal = {Journal of Experimental Medicine},
   month = {2},
   pages = {569-579},
   pmid = {8627168},
   title = {Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells},
   volume = {183},
   year = {1996},
}
@article{Salmi2019,
   abstract = {Significance: Vascular adhesion protein-1 (VAP-1) is an ectoenzyme that oxidates primary amines in a reaction producing also hydrogen peroxide. VAP-1 on the blood vessel endothelium regulates leukocyte extravasation from the blood into tissues under physiological and pathological conditions. Recent Advances: Inhibition of VAP-1 by neutralizing antibodies and by several novel small-molecule enzyme inhibitors interferes with leukocyte trafficking and alleviates inflammation in many experimental models. Targeting of VAP-1 also shows beneficial effects in several other diseases, such as ischemia/reperfusion, fibrosis, and cancer. Moreover, soluble VAP-1 levels may serve as a new prognostic biomarker in selected diseases. Critical Issues: Understanding the contribution of the enzyme activity-independent and enzyme activity-dependent functions, which often appear to be mediated by the hydrogen peroxide production, in the VAP-1 biology will be crucial. Similarly, there is a pressing need to understand which of the VAP-1 functions are regulated through the modulation of leukocyte trafficking, and what is the role of VAP-1 synthesized in adipose and smooth muscle cells. Future Directions: The specificity and selectivity of new VAP-1 inhibitors, and their value in animal models under therapeutic settings need to be addressed. Results from several programs studying the therapeutic potential of VAP-1 inhibition, which now are in clinical trials, will reveal the relevance of this amine oxidase in humans.},
   author = {Marko Salmi and Sirpa Jalkanen},
   doi = {10.1089/ARS.2017.7418},
   issn = {15577716},
   issue = {3},
   journal = {Antioxidants & Redox Signaling},
   keywords = {cancer,hydrogen peroxide,inflammation,leukocyte trafficking},
   month = {1},
   pages = {314},
   pmid = {29065711},
   publisher = {Mary Ann Liebert, Inc.},
   title = {Vascular Adhesion Protein-1: A Cell Surface Amine Oxidase in Translation},
   volume = {30},
   url = {/pmc/articles/PMC6306676/ /pmc/articles/PMC6306676/?report=abstract https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306676/},
   year = {2019},
}
@article{Arvilommi1997,
   abstract = {Vascular adhesion protein-1 (VAP-1) is an endothelial molecule which mediates lymphocyte binding to endothelium in peripheral lymph nodes and at certain sites of inflammation. The expression of VAP-1 in vitro is strongly up-regulated in inflamed tissues, such as gut and skin. The purpose of this work was to examine the factors responsible for this induction of VAP-1. Since the expression of VAP-1 could not be induced in cultured endothelial cells with a large panel of mediators, we used an organ culture technique for the investigation of the regulation of VAP-1 expression in a more physiological micromilieu. Indeed, we found that the expression of endothelial VAP-1 could be up-regulated in human tonsillar tissue with interleukin (IL)-1, IL-4, tumor necrosis factor (TNF-α), interferon (IFN)-γ and lipopolysaccharide, whereas histamine, thrombin, dibutyryl cAMP, N-formyl-Met-Leu-Phe (fMLP) and phorbol 12-myristate 13-acetate (PMA) had no effect. The induced VAP-1 protein was similar in molecular weight to the non-induced VAP-1, suggesting that VAP-1 synthesized de novo carries appropriate carbohydrate moieties. In contrast to tonsil organ culture, similar inductions performed with human appendix showed no up-regulation of VAP-1 expression, indicating that the regulation of VAP-1 expression exhibits organ-selective characteristics. Furthermore, in these tissues the smooth muscle cells, which constitutively express VAP-1, could not be stimulated to alter their level of expression of this molecule. In conclusion, the expression of VAP-1 can be markedly up-regulated with several mediators in tonsil but not in appendix organ culture, whereas cultured endothelial cells cannot be induced to express VAP-1. These results indicate that the expression of VAP-1 is regulated in a tissue- and cell type-selective manner, and a correct micromilieu is required for the up-regulation to occur.},
   author = {Anna Maija Arvilommi and Marko Salmi and Sirpa Jalkanen},
   doi = {10.1002/EJI.1830270730},
   issn = {1521-4141},
   issue = {7},
   journal = {European Journal of Immunology},
   keywords = {Adhesion molecule,Endothelial,Inflammation},
   month = {7},
   pages = {1794-1800},
   pmid = {9247594},
   publisher = {John Wiley & Sons, Ltd},
   title = {Organ-selective regulation of vascular adhesion protein-1 expression in man},
   volume = {27},
   url = {https://onlinelibrary.wiley.com/doi/full/10.1002/eji.1830270730 https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.1830270730 https://onlinelibrary.wiley.com/doi/10.1002/eji.1830270730},
   year = {1997},
}
@article{Salmi2001,
   abstract = {Lymphocytes leave the blood using a sequential adhesion cascade. Vascular adhesion molecule-1 (VAP-1) is a surface-expressed endothelial glycoprotein, which belongs to a distinct subgroup of monoamine oxidases. We show here that catalytic activity of VAP-1 on primary endothelial cells directly regulates lymphocyte rolling under defined laminar shear. VAP-1 seems to bind to a primary amino group presented on the lymphocyte surface and oxidatively deaminate it in a reaction, which results in the formation of a transient covalent bond between the two cell types. Instead, soluble reaction products (aldehydes and hydrogen peroxide) are not needed for the VAP-1-dependent rolling. Enzymatic regulation of lymphocyte adhesion to endothelium provides a previously unrecognized rapid way of controlling the extravasation process.},
   author = {Marko Salmi and Gennady G. Yegutkin and Riikka Lehvonen and Kaisa Koskinen and Tiina Salminen and Sirpa Jalkanen},
   doi = {10.1016/S1074-7613(01)00108-X},
   issn = {1074-7613},
   issue = {3},
   journal = {Immunity},
   month = {3},
   pages = {265-276},
   pmid = {11290336},
   publisher = {Cell Press},
   title = {A Cell Surface Amine Oxidase Directly Controls Lymphocyte Migration},
   volume = {14},
   year = {2001},
}
@article{Yen2024,
   abstract = {Vascular adhesion protein-1 (VAP-1) plays a dual role with its adhesive and enzymatic properties, facilitating leukocyte migration to sites of inflammation and catalyzing the breakdown of primary amines into harmful by-products, which are linked to diabetic complications. Present in various tissues, VAP-1 also circulates in a soluble form in the bloodstream. Diabetes is associated with several complications such as cardiovascular disease, retinopathy, nephropathy, and neuropathy, significantly contributing to disability and mortality. These complications arise from hyperglycemia-induced oxidative stress, inflammation, and the formation of advanced glycation end-products (AGEs). Earlier research, including our own from the 1990s and early 2000s, has underscored the critical role of VAP-1 in these pathological processes, prompting extensive investigation into its contribution to diabetic complications. In this review, we examine the involvement of VAP-1 in diabetes and its complications, alongside its link to other conditions related to diabetes, such as cancer and metabolic dysfunction-associated fatty liver disease. We also explore the utility of soluble VAP-1 as a biomarker for diabetes, its complications, and other related conditions. Since the inhibition of VAP-1 to treat diabetic complications is a novel and promising treatment option, further studies are needed to translate the beneficial effect of VAP-1 inhibitors observed in animal studies to clinical trials recruiting human subjects. Besides, future studies should focus on using serum sVAP-1 levels for risk assessment in diabetic patients, identifying those who need intensive glycemic control, and determining the patient population that would benefit most from VAP-1 inhibitor therapies.},
   author = {I-Weng Yen and Hung-Yuan Li},
   doi = {10.1111/jdi.14209},
   issn = {2040-1124},
   issue = {8},
   journal = {Journal of diabetes investigation},
   keywords = {Vascular adhesion protein‐1,diabetic complications,semicarbazide‐sensitive amine oxidase},
   month = {8},
   pages = {982-989},
   pmid = {38581224},
   publisher = {John Wiley and Sons Inc},
   title = {The role of vascular adhesion protein-1 in diabetes and diabetic complications.},
   volume = {15},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/38581224 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC11292389},
   year = {2024},
}
@article{Li2021,
   abstract = {Vascular adhesion protein-1 (VAP-1) is a semicarbazide-sensitive amine oxidase (SSAO), whose enzymatic activity regulates the adhesion/exudation of leukocytes in/from blood vessels. Due to its abundant expressions in vascular systems and prominent roles in inflammations, increasing attentions have been paid to the roles of VAP-1/SSAO in atherosclerosis, a chronic vascular inflammation that eventually drives clinical cardiovascular events. Clinical studies have demonstrated a potential value of soluble VAP-1 (sVAP-1) for the diagnosis and prognosis of cardiovascular diseases. Recent findings revealed that VAP-1 is expressed in atherosclerotic plaques and treatment with VAP-1 inhibitors alleviates the progression of atherosclerosis. This review will focus on the roles of VAP-1/SSAO in the progression of atherosclerotic lesions and therapeutic potentials of VAP-1 inhibitors for cardiovascular diseases.},
   author = {Hui Li and Shiyu Du and Panpan Niu and Xiaosong Gu and Jun Wang and Ying Zhao},
   doi = {10.3389/FPHAR.2021.679707},
   issn = {1663-9812},
   journal = {Frontiers in pharmacology},
   keywords = {Hui Li,MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PMC8312380,PubMed Abstract,Review,Shiyu Du,Ying Zhao,doi:10.3389/fphar.2021.679707,pmid:34322017},
   month = {7},
   pmid = {34322017},
   publisher = {Front Pharmacol},
   title = {Vascular Adhesion Protein-1 (VAP-1)/Semicarbazide-Sensitive Amine Oxidase (SSAO): A Potential Therapeutic Target for Atherosclerotic Cardiovascular Diseases},
   volume = {12},
   url = {https://pubmed.ncbi.nlm.nih.gov/34322017/},
   year = {2021},
}
@article{Wang2018,
   abstract = {Inflammation, oxidative stress, and the formation of advanced glycated end-products (AGEs) are important components of atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation. Its enzymatic activity, semicarbazide-sensitive amine oxidase (SSAO), can catalyze oxidative deamination reactions to produce hydrogen peroxide and aldehydes, leading to the subsequent generation of AGEs. This study aimed to investigate the effect of VAP-1/SSAO inhibition on atherosclerosis. In our study, immunohistochemical staining showed that atherosclerotic plaques displayed higher VAP-1 expression than normal arterial walls in apolipoprotein E-deficient mice, cholesterol-fed New Zealand White rabbits and humans. In cholesterol-fed rabbits, VAP-1 was expressed on endothelial cells and smooth muscle cells in the thickened intima of the aorta. Treatment with PXS-4728A, a selective VAP-1/SSAO inhibitor, in cholesterol-fed rabbits significantly decreased SSAO-specific hydrogen peroxide generation in the aorta and reduced atherosclerotic plaques. VAP-1/SSAO inhibition also lowered blood low-density lipoprotein cholesterol, reduced the expression of adhesion molecules and inflammatory cytokines, suppressed recruitment and activation of macrophages, and decreased migration and proliferation of SMC. In conclusion, VAP-1/SSAO inhibition reduces atherosclerosis and may act through suppression of several important mechanisms for atherosclerosis.},
   author = {Shu Huei Wang and Tse Ya Yu and Chi Sheng Hung and Chung Yi Yang and Mao Shin Lin and Chien Yin Su and Yuh Lien Chen and Hsien Li Kao and Lee Ming Chuang and Feng Chiao Tsai and Hung Yuan Li},
   doi = {10.1038/s41598-018-27551-6},
   issn = {20452322},
   issue = {1},
   journal = {Scientific Reports},
   month = {12},
   pmid = {29915377},
   publisher = {Nature Publishing Group},
   title = {Inhibition of Semicarbazide-sensitive Amine Oxidase Reduces Atherosclerosis in Cholesterol-fed New Zealand White Rabbits},
   volume = {8},
   year = {2018},
}
@article{Pannecoeck2015,
   abstract = {Vascular adhesion protein-1 (VAP-1) is a member of the copper-containing amine oxidase/ semicarbazide-sensitive amine oxidase (AOC/SSAO) enzyme family. SSAO enzymes catalyze oxidative deamination of primary amines, which results in the production of the corresponding aldehyde, hydrogen peroxide and ammonium. VAP-1 is continuously expressed as a transmembrane glycoprotein in the vascular wall during development and facilitates the accumulation of inflammatory cells into the inflamed environment in concert with other leukocyte adhesion molecules. The soluble form of VAP-1 is released into the circulation mainly from vascular endothelial cells. Over- and under-expression of sVAP-1 result in alterations of the reported reaction product levels, which are involved in the pathogenesis of multiple human diseases. The combination of enzymatic and adhesion capacities as well as its strong association with inflammatory pathologies makes VAP-1 an interesting therapeutic target for drug discovery. In this article, we will review the general characteristics and biological functions of VAP-1, focusing on its important role as a prognostic biomarker in human pathologies. In addition, the potential therapeutic application of VAP-1 inhibitors will be discussed.},
   author = {Roos Pannecoeck and Daphne Serruys and Lara Benmeridja and Joris R. Delanghe and Nanja Van Geel and Reinhart Speeckaert and Marijn M. Speeckaert},
   doi = {10.3109/10408363.2015.1050714},
   issn = {1549781X},
   issue = {6},
   journal = {Critical Reviews in Clinical Laboratory Sciences},
   keywords = {Copper-containing amine oxidase,Drug target,Leukocyte trafficking,Semicarbazide-sensitive amine oxidase,Soluble cell adhesion molecules,VAP-1},
   pages = {284-300},
   pmid = {26287391},
   publisher = {Taylor and Francis Ltd},
   title = {Vascular adhesion protein-1: Role in human pathology and application as a biomarker},
   volume = {52},
   year = {2015},
}
@article{Wang2018,
   abstract = {Inflammation, oxidative stress, and formation of advanced glycated end products (AGEs) and advanced lipoxidation end products (ALEs) are important for atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation and has semicarbazide-sensitive amine oxidase (SSAO) activity, which catalyzes oxidative deamination to produce hydrogen peroxide and aldehydes, leading to generation of AGEs and ALEs. However, the effect of VAP-1/SSAO inhibition on atherosclerosis remains controversial, and no studies used coronary angiography to evaluate if plasma VAP-1/SSAO is a biomarker for coronary artery disease (CAD). Here, we examined if plasma VAP-1/SSAO is a biomarker for CAD diagnosed by coronary angiography in humans and investigated the effect of VAP-1/SSAO inhibition by a specific inhibitor PXS-4728A on atherosclerosis in cell and animal models. In the study, VAP-1/SSAO expression was increased in plaques in humans and in apolipoprotein E (ApoE)-deficient mice, and colocalized with vascular endothelial cells and smooth muscle cells (SMCs). Patients with CAD had higher plasma VAP-1/SSAO than those without CAD. Plasma VAP-1/SSAO was positively associated with the extent of CAD. In ApoE-deficient mice, VAP-1/SSAO inhibition reduced atheroma and decreased oxidative stress. VAP-1/SSAO inhibition attenuated the expression of adhesion molecules, chemoattractant proteins, and proinflammatory cytokines in the aorta, and suppressed monocyte adhesion and transmigration across human umbilical vein endothelial cells. Consequently, the expression of markers for macrophage recruitment and activation in plaques was decreased by VAP-1/SSAO inhibition. Besides, VAP-1/SSAO inhibition suppressed proliferation and migration of A7r5 SMC. Our data suggest that plasma VAP-1/SSAO is a novel biomarker for the presence and the extent of CAD in humans. VAP-1/SSAO inhibition by PXS-4728A is a potential treatment for atherosclerosis.},
   author = {Shu Huei Wang and Tse Ya Yu and Feng Chiao Tsai and Chris J. Weston and Mao Shin Lin and Chi Sheng Hung and Hsien Li Kao and Yu I. Li and Montse Solé and Mercedes Unzeta and Yuh Lien Chen and Lee Ming Chuang and Hung Yuan Li},
   doi = {10.1016/j.trsl.2018.03.001},
   issn = {18781810},
   journal = {Translational Research},
   month = {7},
   pages = {12-31},
   pmid = {29653075},
   publisher = {Mosby Inc.},
   title = {Inhibition of semicarbazide-sensitive amine oxidase reduces atherosclerosis in apolipoprotein E-deficient mice},
   volume = {197},
   year = {2018},
}
@article{Danielli2022,
   abstract = {Vascular adhesion protein-1 (VAP-1) also known as amino oxidase copper containing 3 (AOC3) is a proinflammatory and versatile molecule with adhesive and enzymatic properties. VAP-1 is a primary amine oxidase belonging to the semicarbazide-sensitive amine oxidase (SSAO) family, which catalyzes the oxidation of primary amines leading to the production of ammonium, formaldehyde, methylglyoxal, and hydrogen peroxide. VAP-1 is mainly expressed by endothelial cells, smooth muscle cells, adipocytes and pericytes. It is involved in a repertoire of biological functions, e.g., immune cell extravasation, angiogenesis, and vascularization. Research into VAP-1 has intensified within the last decade on its role as a novel clinical biomarker and as a potential therapeutic target of vascular inflammatory disorders such as atherosclerosis, stroke, diabetes, neurovascular disorders (e.g., Alzheimer's Disease), hepatic disease (e.g., non-alcoholic steatohepatitis), and skin conditions (e.g., psoriasis). This is the most up-to-date and comprehensive review on VAP-1 focusing on the translational aspects of VAP-1. Compared to recent reviews, our review provides novel insights on VAP-1 and heart failure, stroke and frailty, diabetes, endometriosis, osteoarthritis, COVID-19, conjunctivitis associated systemic lupus erythematosus, hematopoietic stem cells, gliomas, treatment of colorectal cancer with a novel VAP-1 inhibitor (U-V269), promoting recovery of motor functions and habit learning with a novel VAP-1 inhibitor (PXS-4681A), and 68Ga-DOTA-Siglec-9, a labelled peptide of Siglec-9 (a VAP-1 ligand), which appears to be a safe PET tracer for inflammation in rheumatoid arthritis. Finally, we present the emerging role of VAP-1 in pregnancy as a gatekeeper of immune cells, which are critical for spiral arterial remodeling, the deficiency of which could lead to vascular disorders of pregnancy such as preeclampsia. Future research should prioritize clinical trials on VAP-1 small-molecule inhibitors and monoclonal antibodies, thus, maximizing the potential of VAP-1 targeted therapy as well as research into sVAP-1 as a clinical biomarker of diseases and its prognosis.},
   author = {Marianna Danielli and Roisin Clare Thomas and Lauren Marie Quinn and Bee Kang Tan},
   doi = {10.1024/0301-1526/a001031},
   issn = {16642872},
   issue = {6},
   journal = {Vasa - European Journal of Vascular Medicine},
   keywords = {Vascular adhesion protein-1,amine oxidase,biomarker,cardiovascular,copper 3,inflammation,semicarbazide-sensitive amine oxidase},
   month = {11},
   pages = {341-350},
   pmid = {36200383},
   publisher = {Hogrefe Verlag GmbH & Co. KG},
   title = {Vascular adhesion protein-1 (VAP-1) in vascular inflammatory diseases: A narrative review},
   volume = {51},
   year = {2022},
}
@article{Murata2017,
   abstract = {Purpose/Aim of the study: To explore the possible role of vascular adhesion protein-1 (VAP-1) via its enzymatic function as a semicarbazide-sensitive amine oxidase (SSAO) in the pathogenesis of proliferative diabetic retinopathy (PDR). Materials and Methods: The levels of soluble VAP-1/SSAO and the unsaturated aldehyde acrolein (ACR)-conjugated protein, Nε-(3-formyl-3, 4-dehydropiperidino) lysine adduct (FDP-Lys), were measured in vitreous fluid samples of PDR and non-diabetic patients using ELISA. Recombinant human VAP-1/SSAO (rhVAP-1/SSAO) was incubated with spermine, with or without semicarbazide or RTU-1096 (a specific inhibitor for VAP-1/SSAO). Immunofluorescence assays were performed to assess the localization of VAP-1/SSAO and FDP-Lys in fibrovascular tissues from patients with PDR. The impact of ACR on cultured retinal capillary endothelial cells was assessed using a cell viability assay and total glutathione (GSH) measurements. Results: The levels of sVAP-1/SSAO and FDP-Lys were elevated in the vitreous fluid of patients with PDR. Incubation of rhVAP-1 with spermine resulted in the generation of hydrogen peroxide and FDP-Lys and the production was inhibited by semicarbazide and RTU-1096. In fibrovascular tissues, FDP-Lys and VAP-1/SSAO were present in endothelial cells. ACR stimulation reduced GSH levels in the cultured endothelial cells in a dose-dependent manner and caused cellular toxicity. Conclusions: Our results indicate the pathological role of sVAP-1/SSAO to generate hydrogen peroxide and toxic aldehyde ACR, both of which are associated with oxidative stress, as a consequence of spermine oxidation in eyes with PDR.},
   author = {Miyuki Murata and Kousuke Noda and Akiko Kawasaki and Shiho Yoshida and Yoko Dong and Michiyuki Saito and Zhenyu Dong and Ryo Ando and Shohei Mori and Wataru Saito and Atsuhiro Kanda and Susumu Ishida},
   doi = {10.1080/02713683.2017.1359847},
   issn = {14602202},
   issue = {12},
   journal = {Current Eye Research},
   keywords = {Acrolein,diabetic retinopathy,hydrogen peroxide,oxidative stress,polyamine},
   month = {12},
   pages = {1674-1683},
   pmid = {28937866},
   publisher = {Taylor and Francis Ltd},
   title = {Soluble Vascular Adhesion Protein-1 Mediates Spermine Oxidation as Semicarbazide-Sensitive Amine Oxidase: Possible Role in Proliferative Diabetic Retinopathy},
   volume = {42},
   year = {2017},
}
@article{Toiyama2009,
   abstract = {Background and Objectives: Vascular adhesion protein-1 (VAP-1) is an endothelial cell molecule that controls leukocyte tissue infiltration. Elevated serum soluble VAP-1 (sVAP-1) has been described in certain diseases with an inflammatory component. However, sVAP-1 expression or function has not been studied in colorectal cancer. The present study determined the relationships between preoperative serum sVAP-1 and clinicopathological features and prognosis in colorectal cancer. Methods: One hundred patients with histologically proven colorectal cancer and 33 normal volunteers were included. Preoperative serum was collected, and sVAP-1 levels were assayed by enzyme-linked immunosorbent assay. Results: Mean sVAP-1 level in patients was significantly higher than in controls, and decreased with disease progression. Mean sVAP-1 level was significantly correlated with venous invasion, lymph node metastasis, distant metastasis including hepatic metastasis, and advanced TNM classification. Furthermore, sVAP-1 was an independent marker for predicting lymph node or hepatic metastasis. Prognosis of patients with a lower sVAP-1 level was significantly worse than those with elevated sVAP-1. Conclusions: Preoperative lowsVAP-1 level is associated with poor prognosis in colorectal cancer. Measuring serum sVAP-1 may provide valuable information in predicting patients with lymph node or hepatic metastasis. © 2009 Wiley-Liss, Inc.},
   author = {Yuji Toiyama and Chikao Miki and Yasuhiro Inoue and Aya Kawamoto and Masato Kusunoki},
   doi = {10.1002/jso.21246},
   issn = {00224790},
   issue = {6},
   journal = {Journal of Surgical Oncology},
   keywords = {Colorectal cancer,Hepatic metastasis,Lymph node metastasis,Prognostic factor,sVAP-1},
   month = {5},
   pages = {368-372},
   pmid = {19204971},
   title = {Circulating form of human vascular adhesion protein-1 (VAP-1): Decreased serum levels in progression of colorectal cancer and predictive marker of lymphatic and hepatic metastasis},
   volume = {99},
   year = {2009},
}
@article{Kurkijarvi2000,
   abstract = {Background and Aims: Vascular adhesion protein 1 (VAP-1) is an endothelial glycoprotein that supports adhesion of lymphocytes to hepatic endothelium and has sequence homology with semicarbazide-sensitive amine oxidases (SSAOs). We investigated whether soluble VAP-1 (sVAP-1) displays SSAO activity and thereby accounts for increased monoamine oxidase activity in the serum of patients with liver diseases. Methods: sVAP-1 concentration and SSAO activity were measured in peripheral, hepatic, and portal blood and in bile from patients with liver disease and in peripheral blood of control subjects, using enzyme-linked immunosorbent assay and enzymatic assays. Results: sVAP-1 concentration (mean [±SE], 143.67 [34.97-92.67] ng/mL) and SSAO activity (18.8 [12.0-24.6] nmol · mL-1> h-1>) were significantly increased in chronic liver diseases compared with healthy controls (87.1 [53.5-127] ng/mL [P < 0.001] and 10.7 [6.5-12.7] nmol · mL-1> · h-1> [P < 0.05]) but not in massive necrosis caused by paracetamol poisoning (109 [80.3-14.0] ng/mL and 8.9 [5.7-12.3] nmol · mL-1> · h-1>). sVAP-1 correlated with serum transaminase and bilirubin but not with creatinine. In 5 paired samples, sVAP-1, concentration was higher in hepatic (median, 113 [range, 53-122]) than in portal vein (102 [42-109]; 2P < 0.05), and was not detected in bile. There was a highly significant correlation between serum sVAP-1 and SSAO activity in normal subjects, patients with acute liver failure, and those with chronic liver disease (r = 0.895; P < 0.001.). When serum was depleted of sVAP-1, by immunoaffinity chromatography, SSAO activity was eliminated. Conclusions: sVAP-1 levels are increased in chronic liver disease, and sVAP-1 is likely derived from the liver. Serum sVAP-1 displays SSAO activity and accounts for most of the monoamine oxidase activity in human serum.},
   author = {Riikka Kurkijarvi and Gennady G. Yegutkin and Bridget K. Gunson and Sirpa Jalkanen and Marko Salmi and David H. Adams},
   doi = {10.1053/gast.2000.18163},
   issn = {00165085},
   issue = {4},
   journal = {Gastroenterology},
   pages = {1096-1103},
   pmid = {11040196},
   title = {Circulating soluble vascular adhesion protein 1 accounts for the increased serum monoamine oxidase activity chronic liver disease},
   volume = {119},
   year = {2000},
}
@article{Yasuda2011,
   abstract = {Background Vascular adhesion protein-1 (VAP-1) regulates leukocyte tissue infiltration. Elevated serum soluble VAP-1 (sVAP-1) levels occur in certain diseases having an inflammatory component. We previously showed in colorectal cancer that sVAP-1 expression is significantly higher relative to controls, and this decreased expression is associated with poor prognosis and lymph node and liver metastasis. However, sVAP-1 expression has not been described for gastric cancer. This study determines the relationship between preoperative serum sVAP-1 levels and clinicopathological features and prognosis in gastric cancer. Methods Preoperative serum was collected from 107 gastric cancer patients and 33 normal controls. sVAP-1 levels were assayed by enzyme-linked immunosorbent assay. Results The mean sVAP-1 level for cancer patients was significantly higher relative to controls, and decreased with disease progression. Tumor size, serosal invasion, lymph node metastasis, peritoneal dissemination, and TNM classification was significantly correlated with sVAP-1 level. sVAP-1 is also an independent predictive marker for lymph node metastasis. Patients having low sVAP-1 levels had significantly poorer prognosis relative to patients having elevated sVAP-1 in all or stages I-III gastric cancer patients, respectively. Conclusions Low sVAP-1 levels are associated with poor prognosis in gastric cancer. Determining sVAP-1 levels may be valuable for predicting prognosis and lymph node metastasis. © 2011 Wiley-Liss, Inc.},
   author = {Hiromi Yasuda and Yuji Toiyama and Masaki Ohi and Yasuhiko Mohri and Chikao Miki and Masato Kusunoki},
   doi = {10.1002/jso.21877},
   issn = {00224790},
   issue = {7},
   journal = {Journal of Surgical Oncology},
   keywords = {gastric cancer,lymph node metastasis,prognostic factor,sVAP-1},
   month = {6},
   pages = {695-699},
   pmid = {21308684},
   title = {Serum soluble vascular adhesion protein-1 is a valuable prognostic marker in gastric cancer},
   volume = {103},
   year = {2011},
}
@article{Börgeson2022,
   abstract = {The prevalence of obesity and metabolic diseases continues to rise, which has led to an increased interest in studying adipose tissue to elucidate underlying disease mechanisms. The use of genetic mouse models has been critical for understanding the role of specific genes for adipose tissue function and the tissue’s impact on other organs. However, mouse adipose tissue displays key differences to human fat, which has led, in some cases, to the emergence of some confounding concepts in the adipose field. Such differences include the depot-specific characteristics of visceral and subcutaneous fat, and divergences in thermogenic fat phenotype between the species. Adipose tissue characteristics may therefore not always be directly compared between species, which is important to consider when setting up new studies or interpreting results. This mini review outlines our current knowledge about the cell biological differences between human and mouse adipocytes and fat depots, highlighting some examples where inadequate knowledge of species-specific differences can lead to confounding results, and presenting plausible anatomic explanations that may underlie the differences. The article thus provides critical insights and guidance for researchers working primarily with only human or mouse fat tissue, and may contribute to new ideas or concepts in the important and evolving field of adipose biology.},
   author = {Emma Börgeson and Jeremie Boucher and Carolina E. Hagberg},
   doi = {10.3389/FCELL.2022.1003118/BIBTEX},
   issn = {2296634X},
   journal = {Frontiers in Cell and Developmental Biology},
   keywords = {adipose tissue,hypertrophy,metabolism,obesity,species differences},
   month = {9},
   pages = {1003118},
   publisher = {Frontiers Media S.A.},
   title = {Of mice and men: Pinpointing species differences in adipose tissue biology},
   volume = {10},
   year = {2022},
}
@article{Chusyd2016,
   abstract = {The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue (WAT) development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of WAT. Thus, further research is warranted to more carefully define the strengths and limitations of rodent WAT as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat.},
   author = {Daniella E. Chusyd and Donghai Wang and Derek M. Huffman and Tim R. Nagy},
   doi = {10.3389/FNUT.2016.00010},
   issn = {2296861X},
   journal = {Frontiers in Nutrition},
   keywords = {fat depot,fat distribution,fat pads,humans,obesity,rodents},
   month = {4},
   publisher = {Frontiers Media S.A.},
   title = {Relationships between Rodent White Adipose Fat Pads and Human White Adipose Fat Depots},
   volume = {3},
   year = {2016},
}
@article{Chait2020,
   abstract = {Adipose tissue plays essential roles in maintaining lipid and glucose homeostasis. To date several types of adipose tissue have been identified, namely white, brown, and beige, that reside in various specific anatomical locations throughout the body. The cellular composition, secretome, and location of these adipose depots define their function in health and metabolic disease. In obesity, adipose tissue becomes dysfunctional, promoting a pro-inflammatory, hyperlipidemic and insulin resistant environment that contributes to type 2 diabetes mellitus (T2DM). Concurrently, similar features that result from adipose tissue dysfunction also promote cardiovascular disease (CVD) by mechanisms that can be augmented by T2DM. The mechanisms by which dysfunctional adipose tissue simultaneously promote T2DM and CVD, focusing on adipose tissue depot-specific adipokines, inflammatory profiles, and metabolism, will be the focus of this review. The impact that various T2DM and CVD treatment strategies have on adipose tissue function and body weight also will be discussed.},
   author = {Alan Chait and Laura J. den Hartigh},
   doi = {10.3389/FCVM.2020.00022},
   issn = {2297055X},
   journal = {Frontiers in Cardiovascular Medicine},
   keywords = {adipokines,beige adipose tissue,brown adipose tissue,insulin resistance,metabolic syndrome,subcutaneous white adipose tissue,visceral white adipose tissue},
   month = {2},
   pmid = {32158768},
   publisher = {Frontiers Media S.A.},
   title = {Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease},
   volume = {7},
   year = {2020},
}
@article{Blondin2020,
   abstract = {Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β3-adrenergic receptor (β3-AR), the adrenergic receptor believed to mediate BAT thermogenesis, have historically performed poorly in human clinical trials. Here we report that, in contrast to rodents, human BAT thermogenesis is not mediated by the stimulation of β3-AR. Oral administration of the β3-AR agonist mirabegron only elicited increases in BAT thermogenesis when ingested at the maximal allowable dose. This led to off-target binding to β1-AR and β2-AR, thereby increasing cardiovascular responses and white adipose tissue lipolysis, respectively. ADRB2 was co-expressed with UCP1 in human brown adipocytes. Pharmacological stimulation and inhibition of the β2-AR as well as knockdown of ADRB1, ADRB2, or ADRB3 in human brown adipocytes all confirmed that BAT lipolysis and thermogenesis occur through β2-AR signaling in humans (ClinicalTrials.gov NCT02811289). Blondin et al. reveal that therapeutic doses of the β3-AR agonist mirabegron do not stimulate human BAT. Biopsies from participants show that the lack of effect may be explained by the absence of β3-AR and primary expression of β2-AR. In human brown adipocytes, β2-AR agonism increases respiration, whereas pharmacological and genetic inhibition of β2-AR decrease respiration.},
   author = {Denis P. Blondin and Soren Nielsen and Eline N. Kuipers and Mai C. Severinsen and Verena H. Jensen and Stéphanie Miard and Naja Z. Jespersen and Sander Kooijman and Mariëtte R. Boon and Mélanie Fortin and Serge Phoenix and Frédérique Frisch and Brigitte Guérin and Éric E. Turcotte and François Haman and Denis Richard and Frédéric Picard and Patrick C.N. Rensen and Camilla Scheele and André C. Carpentier},
   doi = {10.1016/J.CMET.2020.07.005},
   issn = {19327420},
   issue = {2},
   journal = {Cell Metabolism},
   keywords = {brown adipocyte,brown adipose tissue,cold-induced thermogenesis,energy metabolism,mirabegron,positron emission tomography,β2-adrenergic receptor},
   month = {8},
   pages = {287-300.e7},
   pmid = {32755608},
   publisher = {Cell Press},
   title = {Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation},
   volume = {32},
   year = {2020},
}
@article{Belligoli2019,
   abstract = {Although obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients.},
   author = {Anna Belligoli and Chiara Compagnin and Marta Sanna and Francesca Favaretto and Roberto Fabris and Luca Busetto and Mirto Foletto and Chiara Dal Prà and Roberto Serra and Luca Prevedello and Chiara Da Re and Romeo Bardini and Claudia Mescoli and Massimo Rugge and Paola Fioretto and Scilla Conci and Silvia Bettini and Gabriella Milan and Roberto Vettor},
   doi = {10.1038/S41598-019-47719-Y},
   issn = {20452322},
   issue = {1},
   journal = {Scientific reports},
   month = {8},
   pages = {11333},
   pmid = {31383894},
   publisher = {NLM (Medline)},
   title = {Characterization of subcutaneous and omental adipose tissue in patients with obesity and with different degrees of glucose impairment},
   volume = {9},
   year = {2019},
}
@article{2019,
   abstract = {Background: Methylamine, a natural soluble amine present in foods, is known to be a substrate of primary amine oxidase (PrAO) widely expressed in animal tissues. Methylamine has been reported to activate glucose transport in fat cells and to facilitate glucose disposal in rabbits but the interests and limits of such insulin-mimicking actions have not been further explored. This work aimed to perform a preclinical study of the inter-individual variations of these biological properties to study the putative link between PrAO activity and insulin resistance. Methods: Methylamine was tested on human adipocyte preparations and in rabbit pancreatic islets to determine its influence on glucose uptake and insulin release, respectively. PrAO activity and related responses were determined in adipose tissues obtained from two cohorts of non-obese and obese women. Results: Adipose tissue PrAO activity was negatively correlated with insulin resistance in high-risk obese women. PrAO-dependent activation of glucose uptake was negatively correlated with body mass index and reflected the decrease of insulin responsiveness of human fat cells with increasing obesity. Methylamine exhibited antilipolytic properties in adipocytes but was unable to directly activate insulin secretion in isolated pancreatic islets. Conclusions: PrAO activation by its substrates, e.g., methylamine, increases glucose utilization in human adipocytes in a manner that is linked to insulin responsiveness. Methylamine/PrAO interaction can therefore contribute to adipose tissue enlargement but should be considered as potentially useful for diabetes prevention since it could limit lipotoxicity and facilitate glucose handling, at the expense of favoring healthy fat accumulation.},
   author = {Christian Carpéné and Pascale Mauriège and Nathalie Boulet and Simon Biron and Jean-Louis Grolleau and Maria José Garcia-Barrado and Mari Carmen Iglesias-Osma},
   doi = {10.3390/MEDICINES6030089},
   issue = {3},
   journal = {Medicines},
   keywords = {adipose tissue,amine oxidase,glucose transport,insulin sensitivity,obesity,semicarbazide},
   month = {8},
   pages = {89},
   pmid = {31409018},
   publisher = {Multidisciplinary Digital Publishing Institute  (MDPI)},
   title = {Methylamine Activates Glucose Uptake in Human Adipocytes Without Overpassing Action of Insulin or Stimulating its Secretion in Pancreatic Islets},
   volume = {6},
   url = {/pmc/articles/PMC6789716/ /pmc/articles/PMC6789716/?report=abstract https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789716/},
   year = {2019},
}
@article{Iglesias-Osma2004,
   abstract = {Benzylamine, a substrate of semicarbazide-sensitive amine oxidase (SSAO), stimulates glucose transport in rat adipocytes and improves glucose disposal in diabetic rats only in the presence of vanadate. These effects have been described to result from a synergism between the hydrogen peroxide formed during amine oxidation and vanadate, via the generation of pervanadate, a powerful insulin mimicker. However, it has also been reported that benzylamine alone can stimulate glucose uptake and inhibit lipolysis in human fat cells. In this work, we therefore investigated whether benzylamine on its own was able to induce both in vivo and in vitro insulin-like responses in animal models other than rat. In rabbits, the i.v. infusion of 7 μmol/kg benzylamine before a glucose tolerance test resulted in a net reduction of the hyperglycemic response without a change in insulin secretion. Benzylamine also improved glucose tolerance and reduced lipid mobilization in hyperglycemic/obese mice. In vitro, 0.1 mM benzylamine stimulated glucose transport and inhibited lipolysis in mouse and rabbit adipocytes. These effects were blocked by previous treatments with semicarbazide, a SSAO inhibitor. Levels of benzylamine oxidation were more elevated in mouse than in rabbit adipose tissues, whereas the reverse was observed for skeletal muscles. Finally, benzylamine was unable to stimulate insulin secretion by isolated pancreatic islets from both species and SSAO activity was hardly detectable in pancreas. Together, our results bring evidence that benzylamine on its own can improve glucose tolerance in rabbit and mouse, likely by stimulating glucose uptake via amine oxidase activation in insulin-sensitive tissues.},
   author = {María Carmen Iglesias-Osma and Maria José Garcia-Barrado and Virgile Visentin and Maria Francisca Pastor-Mansilla and Sandy Bour and Daníelle Prévot and Philippe Valet and Julio Moratinos and Christian Carpéné},
   doi = {10.1124/JPET.103.063636},
   issn = {0022-3565},
   issue = {3},
   journal = {The Journal of pharmacology and experimental therapeutics},
   keywords = {Adipocytes / drug effects*,Adipocytes / metabolism,Animals,Benzylamines / pharmacology*,Biological Transport / drug effects,Carcinogens / pharmacology,Christian Carpéné,Diabetes Mellitus,Drug Interactions,Experimental / blood,Experimental / metabolism*,Glucose / metabolism*,Glucose Tolerance Test,Infusions,Insulin / blood,Insulin / pharmacology,Intravenous,Islets of Langerhans / drug effects,Lipolysis / drug effects*,MEDLINE,Maria José Garcia-Barrado,María Carmen Iglesias-Osma,Mice,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,Oxidation-Reduction / drug effects,PubMed Abstract,Rabbits,Research Support,Semicarbazides / pharmacology,Starvation / blood,doi:10.1124/jpet.103.063636,pmid:14978192},
   month = {6},
   pages = {1020-1028},
   pmid = {14978192},
   publisher = {J Pharmacol Exp Ther},
   title = {Benzylamine exhibits insulin-like effects on glucose disposal, glucose transport, and fat cell lipolysis in rabbits and diabetic mice},
   volume = {309},
   url = {https://pubmed.ncbi.nlm.nih.gov/14978192/},
   year = {2004},
}
@article{Zorzano2003,
   abstract = {Semicarbazide-sensitive amine oxidase (SSAO) is very abundant at the plasma membrane in adipocytes. The combination of SSAO substrates and low concentrations of vanadate markedly stimulates glucose transport and GLUT4 glucose transporter recruitment to the cell surface in rat adipocytes by a mechanism that requires SSAO activity and hydrogen peroxide formation. Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin-receptor substrates 1 (IRS-1) and 3 (IRS-3) and phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipose cells, which occurs in the presence of a weak stimulation of insulin-receptor kinase. Moreover, the acute administration of benzylamine and vanadate in vivo enhances glucose tolerance in non-diabetic and streptozotocin-induced diabetic rats and reduces hyperglycemia after chronic treatment in streptozotocin-diabetic rats. Based on these observations, we propose that SSAO activity and vanadate potently mimic insulin effects in adipose cells and exert an anti-diabetic action in an animal model of type 1 diabetes mellitus. © 2003 Elsevier Science B.V. All rights reserved.},
   author = {Antonio Zorzano and Anna Abella and Luc Marti and Christian Carpéné and Manuel Palacín and Xavier Testar},
   doi = {10.1016/S1570-9639(03)00039-6},
   issn = {15709639},
   issue = {1-2},
   journal = {Biochimica et Biophysica Acta - Proteins and Proteomics},
   keywords = {Adipocyte,GLUT4,Glucose transport,Phosphatidylinositol 3-kinase,SSAO,VAP-1},
   month = {4},
   pages = {3-9},
   pmid = {12686100},
   publisher = {Elsevier},
   title = {Semicarbazide-sensitive amine oxidase activity exerts insulin-like effects on glucose metabolism and insulin-signaling pathways in adipose cells},
   volume = {1647},
   year = {2003},
}
@article{Mercader2011,
   abstract = {An enzyme hitherto named semicarbazide-sensitive amine oxidase (SSAO), involved in the oxidation of primary amines, is abundantly expressed in adipocytes. Although SSAO physiological functions remain unclear, several molecules inhibiting its activity have been described to limit fat accumulation in preadipocyte cultures or to reduce body weight gain in obese rodents. Here, we studied whether oral administration of semicarbazide, a prototypical SSAO inhibitor, limits fat deposition in mice. Prolonged treatment with semicarbazide at 0.125% in drinking water limited food and water consumption, hampered weight gain, and deeply impaired fat deposition. The adiposomatic index was reduced by 31%, while body mass was reduced by 15%. Such treatment completely inhibited SSAO, but did not alter MAO activity in white adipose tissue. Consequently, the insulin-like action of the SSAO substrate benzylamine on glucose transport was abolished in adipocytes from semicarbazide-drinking mice, while their insulin sensitivity was not altered. Although semicarbazide is currently considered as a food contaminant with deleterious effects, the SSAO inhibition it induces appears as a novel concept to modulate adipose tissue development, which is promising for antiobesity drug discovery. © 2011 Josep Mercader et al.},
   author = {Josep Mercader and Zsuzsa Iffiú-Soltész and Sandy Bour and Christian Carpéné},
   doi = {10.1155/2011/475786},
   issn = {2090-0716},
   issue = {1},
   journal = {Journal of Obesity},
   month = {1},
   pages = {475786},
   publisher = {John Wiley & Sons, Ltd},
   title = {Oral Administration of Semicarbazide Limits Weight Gain together with Inhibition of Fat Deposition and of Primary Amine Oxidase Activity in Adipose Tissue},
   volume = {2011},
   url = {https://onlinelibrary.wiley.com/doi/full/10.1155/2011/475786 https://onlinelibrary.wiley.com/doi/abs/10.1155/2011/475786 https://onlinelibrary.wiley.com/doi/10.1155/2011/475786},
   year = {2011},
}
@article{Chew2023,
   abstract = {Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and non-alcoholic fatty liver disease [NAFLD]). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the greatest increase in high socio-demographic index (SDI) countries. Mortality rates decreased over time in hyperlipidemia, hypertension, and NAFLD, but not in T2DM and obesity. The highest mortality was found in the World Health Organization Eastern Mediterranean region, and low to low-middle SDI countries. The global prevalence of metabolic diseases has risen over the past two decades regardless of SDI. Urgent attention is needed to address the unchanging mortality rates attributed to metabolic disease and the entrenched sex-regional-socioeconomic disparities in mortality.},
   author = {Nicholas W.S. Chew and Cheng Han Ng and Darren Jun Hao Tan and Gwyneth Kong and Chaoxing Lin and Yip Han Chin and Wen Hui Lim and Daniel Q. Huang and Jingxuan Quek and Clarissa Elysia Fu and Jieling Xiao and Nicholas Syn and Roger Foo and Chin Meng Khoo and Jiong Wei Wang and Georgios K. Dimitriadis and Dan Yock Young and Mohammad Shadab Siddiqui and Carolyn S.P. Lam and Yibin Wang and Gemma A. Figtree and Mark Y. Chan and David E. Cummings and Mazen Noureddin and Vincent Wai Sun Wong and Ronald Ching Wan Ma and Christos S. Mantzoros and Arun Sanyal and Mark Dhinesh Muthiah},
   doi = {10.1016/j.cmet.2023.02.003},
   issn = {19327420},
   issue = {3},
   journal = {Cell Metabolism},
   keywords = {diabetes mellitus,disability-adjusted life years,disparity,global burden,global burden of disease,hypertension,metabolic disease,mortality,non-alcoholic fatty liver disease,obesity},
   month = {3},
   pages = {414-428.e3},
   pmid = {36889281},
   publisher = {Cell Press},
   title = {The global burden of metabolic disease: Data from 2000 to 2019},
   volume = {35},
   url = {http://www.cell.com/article/S1550413123000396/fulltext http://www.cell.com/article/S1550413123000396/abstract https://www.cell.com/cell-metabolism/abstract/S1550-4131(23)00039-6},
   year = {2023},
}
@article{Ma2011,
   abstract = {The systemic immune response has a vital role in propagating the damage of an intracerebral hemorrhage (ICH). Vascular adhesion protein-1 (VAP-1), a semicarbazide (SCZ)-sensitive-amine-oxidase, was found in previous studies to have a role in migration of immune cells. In this study, we hypothesize that VAP-1 inhibition may decrease brain injury by attenuating the transmigration of immune cells to the injury site, and by doing so, reduce cerebral edema and improve neurobehavioral function in mice. Two VAP-1 inhibitors, LJP1586 and SCZ were given 1 hour after ICH induction by either collagenase or autologous blood injection. The VAP-1 siRNA, a VAP-1 gene silencer, and human recombinant AOC3 protein, a VAP-1 analogue, were delivered by intracerebroventricular injection. Postassessment included neurobehavioral testing, brain edema measurement, quantification of neutrophil infiltration and microglia/macrophage activation, and measurement of intercellular adhesion molecule-1 (ICAM-1), P-selectin, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) expression 24 hours after ICH. We found that LJP1586 and SCZ reduced brain edema and neurobehavioral deficits 24 hours after ICH induction. These two drugs were also found to decrease levels of ICAM-1, MCP-1, TNF-α, and inhibit neutrophilic infiltration and microglia/macrophage activation. We conclude that VAP-1 inhibition provided antiinflammation effect by reducing adhesion molecule expression and immune cell infiltration after ICH. © 2011 ISCBFM All rights reserved.},
   author = {Qingyi Ma and Anatol Manaenko and Nikan H. Khatibi and Wanqiu Chen and John H. Zhang and Jiping Tang},
   doi = {10.1038/JCBFM.2010.167},
   issn = {1559-7016},
   issue = {3},
   journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism},
   keywords = {Allylamine / administration & dosage,Allylamine / analogs & derivatives*,Allylamine / antagonists & inhibitors,Amine Oxidase (Copper-Containing) / administration & dosage,Amine Oxidase (Copper-Containing) / antagonists & inhibitors*,Amine Oxidase (Copper-Containing) / genetics,Anatol Manaenko,Animal / drug effects,Animals,Behavior,Brain Edema / pathology,Cell Adhesion Molecules / administration & dosage,Cell Adhesion Molecules / antagonists & inhibitors*,Cell Adhesion Molecules / genetics,Chemokine CCL2 / metabolism,Down-Regulation,Extramural,Gene Silencing,Humans,Inbred Strains,Inflammation / etiology*,Inflammation / prevention & control*,Injections,Intercellular Adhesion Molecule-1 / metabolism,Intracranial Hemorrhages / complications*,Intracranial Hemorrhages / pathology,Intracranial Hemorrhages / physiopathology,Intracranial Hemorrhages / psychology,Intraperitoneal,Intraventricular,Jiping Tang,MEDLINE,Male,Mice,N.I.H.,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Nervous System / drug effects,Nervous System / physiopathology,Neutrophil Infiltration / drug effects,PMC3063621,PubMed Abstract,Qingyi Ma,RNA,Recombinant Proteins / administration & dosage,Research Support,Semicarbazides / administration & dosage,Small Interfering / administration & dosage,Stroke / complications*,Stroke / etiology,Tumor Necrosis Factor-alpha / metabolism,doi:10.1038/jcbfm.2010.167,pmid:20877383},
   pages = {881-893},
   pmid = {20877383},
   publisher = {J Cereb Blood Flow Metab},
   title = {Vascular adhesion protein-1 inhibition provides antiinflammatory protection after an intracerebral hemorrhagic stroke in mice},
   volume = {31},
   url = {https://pubmed.ncbi.nlm.nih.gov/20877383/},
   year = {2011},
}
@article{Xu2014,
   abstract = {Aneurysmal subarachnoid hemorrhage (SAH) is a potentially devastating clinical problem. Despite advances in the diagnosis and treatment of SAH, outcome remains unfavorable. An increased inflammatory state, one that is characterized by enhanced leukocyte trafficking has been reported to contribute to neuronal injury in association with multiple brain insults, including hemorrhagic and ischemic stroke. This study was designed to investigate, in rats, the neuropathologic consequences of heightened leukocyte trafficking following SAH, induced via endovascular perforation of the anterior cerebral artery. Experiments focused on the initial 48 h post-SAH and sought to establish whether blockade of vascular adhesion protein-1 (VAP-1), with LJP-1586, was able to provide dose-dependent neuroprotection. Treatment with LJP-1586 was initiated at 6 h post-SAH. An intravital microscopy and closed cranial window system, that permitted examination of temporal patterns of rhodamine-6G-labeled leukocyte adhesion/extravasation, was used. Effects of LJP-1586 on neurologic outcomes and leukocyte trafficking at 24 h and 48 h post-SAH were examined. In VAP-1-inhibited vs control rats, results revealed a significant attenuation in leukocyte trafficking at both 24 h and 48 h after SAH, along with an improvement in neurologic outcome. In conclusion, our findings support the involvement of an amplified inflammatory state, characterized by enhanced leukocyte trafficking, during the first 48 h after SAH. VAP-1 blockade yielded neuroprotection that was associated with an attenuation of leukocyte trafficking and improved neurologic outcome..},
   author = {Hao Liang Xu and Maggie Garcia and Fernando Testai and Francesco Vetri and Alexandra Barabanova and Dale A. Pelligrino and Chanannait Paisansathan},
   doi = {10.1016/J.BRAINRES.2014.08.036},
   issn = {1872-6240},
   journal = {Brain research},
   keywords = {Allylamine / analogs & derivatives*,Allylamine / pharmacology,Allylamine / therapeutic use,Amine Oxidase (Copper-Containing) / antagonists & inhibitors,Amine Oxidase (Copper-Containing) / metabolism*,Animal,Animals,Cell Adhesion / drug effects,Cell Adhesion Molecules / antagonists & inhibitors,Cell Adhesion Molecules / metabolism*,Chanannait Paisansathan,Disease Models,Dose-Response Relationship,Drug,Enzyme Inhibitors / pharmacology,Enzyme Inhibitors / therapeutic use,Extramural,Hao-Liang Xu,Leukocytes / drug effects,MEDLINE,Maggie Garcia,Male,N.I.H.,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Nervous System Diseases / drug therapy*,Nervous System Diseases / etiology*,PubMed Abstract,Rats,Research Support,Sprague-Dawley,Subarachnoid Hemorrhage / complications*,Subarachnoid Hemorrhage / pathology,Time Factors,doi:10.1016/j.brainres.2014.08.036,pmid:25175836},
   month = {10},
   pages = {83-89},
   pmid = {25175836},
   publisher = {Brain Res},
   title = {Pharmacologic blockade of vascular adhesion protein-1 lessens neurologic dysfunction in rats subjected to subarachnoid hemorrhage},
   volume = {1586},
   url = {https://pubmed.ncbi.nlm.nih.gov/25175836/},
   year = {2014},
}
@article{Silvola2016,
   abstract = {Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms. In low-density lipoprotein receptor-deficient mice expressing only apolipoprotein B100 (LDLR -/- ApoB100/100), VAP-1 was expressed on endothelial cells lining inflamed atherosclerotic lesions; normal vessel walls in aortas of C57BL/6N control mice were VAP-1-negative. Second, we discovered that the focal uptake of VAP-1 targeting sialic acid-binding immunoglobulin-like lectin 9 based PET tracer [68Ga]DOTA-Siglec-9 in atherosclerotic plaques was associated with the density of activated macrophages (r = 0.58, P = 0.022). As a final point, we found that the inhibition of VAP-1 activity with small molecule LJP1586 decreased the density of macrophages in inflamed atherosclerotic plaques in mice. Our results suggest for the first time VAP-1 as a potential imaging target for inflamed atherosclerotic plaques, and corroborate VAP-1 inhibition as a therapeutic approach in the treatment of atherosclerosis.},
   author = {Johanna M.U. Silvola and Helena Virtanen and Riikka Siitonen and Sanna Hellberg and Heidi Liljenbäck and Olli Metsälä and Mia Ståhle and Tiina Saanijoki and Meeri Käkelä and Harri Hakovirta and Seppo Ylä-Herttuala and Pekka Saukko and Matti Jauhiainen and Tibor Z. Veres and Sirpa Jalkanen and Juhani Knuuti and Antti Saraste and Anne Roivainen},
   doi = {10.1038/SREP35089},
   issn = {2045-2322},
   journal = {Scientific reports},
   keywords = {1-Ring,Adult,Amine Oxidase (Copper-Containing) / metabolism*,Animals,Anne Roivainen,Antigens,Apolipoprotein B-100 / metabolism,Atherosclerotic / diagnostic imaging,Atherosclerotic / metabolism*,Atherosclerotic / pathology,CD / metabolism,Carotid Stenosis / diagnostic imaging,Carotid Stenosis / metabolism,Carotid Stenosis / pathology,Cell Adhesion Molecules / metabolism*,Female,Gallium Radioisotopes,Helena Virtanen,Heterocyclic Compounds,Humans,Inbred C57BL,Johanna M U Silvola,Knockout,LDL / deficiency,LDL / genetics,MEDLINE,Male,Mice,Middle Aged,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,PMC5059718,Plaque,Positron Emission Tomography Computed Tomography,PubMed Abstract,Radioligand Assay,Receptors,Research Support,Sialic Acid Binding Immunoglobulin-like Lectins / metabolism,doi:10.1038/srep35089,pmid:27731409},
   month = {10},
   pmid = {27731409},
   publisher = {Sci Rep},
   title = {Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques},
   volume = {6},
   url = {https://pubmed.ncbi.nlm.nih.gov/27731409/},
   year = {2016},
}
@article{Yang2011,
   abstract = {Aims: This study tested the hypothesis that the inhibition of semicarbazide-sensitive amine oxidase (SSAO) after ischemia could attenuate myocardial ischemia-reperfusion (I/R) injury. Main methods: Anesthetized male Sprague-Dawley rats underwent myocardial I/R injury. Saline, semicarbazide (SCZ, 30 mg/kg), hydralazine (HYD, 10 mg/kg), or LJP 1207 (30 mg/kg) was administered intraperitoneally 3 min before reperfusion. After 30 min of ischemia and 180 min of reperfusion, the myocardial infarct size was determined using nitroblue tetrazolium staining. Myocardial myeloperoxidase activity was determined through biochemical assay. HE staining was used for histopathological evaluation. Myocardial SSAO activity was assayed with high performance liquid chromatography analysis. Additionally, the endothelial expression of P-selectin was evaluated using immunohistochemistry after 30 min of ischemia and 20 min of reperfusion. Key findings: Myocardial SSAO activity was increased in myocardial I/R injury. Administration of SCZ, HYD, or LJP 1207 reduced the myocardial infarct size and decreased leukocyte infiltration and endothelial P-selectin expression in myocardial I/R injury in vivo. Significance: These data suggest that myocardial I/R injury up-regulates myocardial SSAO activity, and the inhibition of SSAO prior to reperfusion is able to attenuate acute myocardial I/R injury. © 2010 Elsevier Inc.},
   author = {Wei Yang and Hui Li and Hongjun Luo and Wenhong Luo},
   doi = {10.1016/J.LFS.2010.12.003},
   issn = {1879-0631},
   issue = {7-8},
   journal = {Life sciences},
   keywords = {Amine Oxidase (Copper-Containing) / analysis,Amine Oxidase (Copper-Containing) / antagonists & inhibitors*,Amine Oxidase (Copper-Containing) / physiology,Animal,Animals,Blood Pressure / drug effects,Chromatography,Disease Models,Heart Rate / drug effects,High Pressure Liquid,Hui Li,Hydralazine / pharmacology,Hydrazines / pharmacology,MEDLINE,Male,Myocardial Infarction / metabolism,Myocardial Infarction / physiopathology,Myocardial Reperfusion Injury / drug therapy*,Myocardial Reperfusion Injury / metabolism,Myocardial Reperfusion Injury / physiopathology,Myocardium / enzymology,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,P-Selectin / analysis,P-Selectin / biosynthesis,Peroxidase / analysis,PubMed Abstract,Rats,Research Support,Semicarbazides / pharmacology,Semicarbazides / therapeutic use*,Sprague-Dawley,Wei Yang,Wenhong Luo,doi:10.1016/j.lfs.2010.12.003,pmid:21146547},
   month = {2},
   pages = {302-306},
   pmid = {21146547},
   publisher = {Life Sci},
   title = {Inhibition of semicarbazide-sensitive amine oxidase attenuates myocardial ischemia-reperfusion injury in an in vivo rat model},
   volume = {88},
   url = {https://pubmed.ncbi.nlm.nih.gov/21146547/},
   year = {2011},
}
@article{Yu2002,
   abstract = {Aims/hypothesis. Semicarbazide-sensitive amine oxidase has been recognised to be a potential risk factor in vascular disorders associated with diabetic complications and to be related to mortality in patients suffering from heart disease. This enzyme, associated with the vascular system, catalyses the deamination of methylamine and aminoacetone, and also acts as an adhesion molecule related to leucocyte trafficking and inflammation. The deaminated products include the toxic aldehydes, formaldehyde and methylglyoxal, respectively, hydrogen peroxide and ammonia. Materials and methods. In this study, the KKAy mouse, a strain possessing features closely resembling those of Type II (non-insulin-dependent) diabetes mellitus has been used to substantiate the hypothesis. Vascular lesions were induced via chronic feeding of a high cholesterol diet. Results. Both MDL-72974A, a selective mechanism-based semicarbazide-sensitive amine oxidase inhibitor and aminoguanidine effectively inhibited aorta semicarbazide-sensitive amine oxidase activity, and caused a substantial increase in urinary methylamine, and a decrease in formaldehyde and methylgloxal levels. Inhibition of semicarbazide-sensitive amine oxidase also reduced oxidative stress, as shown by a reduction of malondialdehyde excretion. Both MDL-72974A and aminoguanidine reduced albuminuria, proteinuria and the number of atherosclerotic lesions in animals fed with a cholesterol diet over a period of treatment for 16 weeks. Conclusion/interpretation. Increased semicarbazide-sensitive amine oxidase-mediated deamination could be involved in the cascade of atherogenesis related to diabetic complications.},
   author = {P. Yu and M. Wang and Y. Deng and H. Fan and L. Shira-Bock},
   doi = {10.1007/S00125-002-0903-9},
   issn = {0012186X},
   issue = {9},
   journal = {Diabetologia},
   keywords = {Aminoguanidine,Atherosclerosis,Formaldehyde,Methylamine,Methylglyoxal,SSAO inhibitor,Semicarbazide-sensitive amine oxidase (SSAO)},
   pages = {1255-1262},
   pmid = {12242458},
   title = {Involvement of semicarbazide-sensitive amine oxidase-mediated deamination in atherogenesis in KKAy diabetic mice fed with high cholesterol diet},
   volume = {45},
   year = {2002},
}
@article{Yu2004,
   abstract = {Semicarbazide-sensitive amine oxidase (SSAO) is located on outer surfaces of adipocytes and endothelial and vascular smooth muscle cells. This enzyme catalyzes deamination of methylamine and aminoacetone, leading to production of toxic formaldehyde and methylglyoxal, respectively, as well as hydrogen peroxide and ammonium. Several lines of evidence suggest that increased SSAO activity is related to chronic inflammation and vascular disorders related to diabetic complications. We found that a highly potent and selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine (FPFA), was capable of reducing numbers of atherosclerotic lesions as well as weight gain in obese KKAy mice fed an atherogenic diet. SSAO inhibitors cause a moderate and long-lasting hyperglycemia. Such an increase in serum glucose is a result of reduction of glucose uptake by adipocytes. SSAO-mediated deamination of endogenous methylamine substrates induces adipocyte glucose uptake and lipogenesis. Highly selective SSAO inhibitors can effectively block induced glucose uptake. The results suggest that increased SSAO-mediated deamination may be concomitantly related to obesity and vascular disorders associated with type 2 diabetes.},
   author = {Peter H. Yu and Michael Wang and Hui Fan and Yulin Deng and Diana Gubisne-Haberle},
   doi = {10.1152/AJPENDO.00272.2003},
   issn = {01931849},
   issue = {4 49-4},
   journal = {American Journal of Physiology - Endocrinology and Metabolism},
   keywords = {Diabetic complications,Glucose uptake,Methylamine,Obesity,Semicarbazide-sensitive amine oxidase},
   month = {4},
   pmid = {14656718},
   title = {Involvement of SSAO-mediated deamination in adipose glucose transport and weight gain in obese diabetic KKAy mice},
   volume = {286},
   year = {2004},
}
@article{Carpéné2019,
   abstract = {Background: Two classes of amine oxidases are found in mammals: those with a flavin adenine dinucleotide as a cofactor, such as monoamine oxidases (MAO) and lysine-specific demethylases (LSD), and those with copper as a cofactor, including copper-containing amine oxidases (AOC) and lysyl oxidases (LOX). All are expressed in adipose tissue, including a semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) strongly present on the adipocyte surface. Methods: Previously, irreversible MAO inhibitors have been reported to limit food intake and/or fat extension in rodents; however, their use for the treatment of depressed patients has not revealed a clear anti-obesity action. Semicarbazide and other molecules inhibiting SSAO/VAP-1 also reduce adiposity in obese rodents. Results: Recently, a LOX inhibitor and a subtype-selective MAO inhibitor have been shown to limit fattening in high-fat diet-fed rats. Phenelzine, which inhibits MAO and AOC, limits adipogenesis in cultured preadipocytes and impairs lipogenesis in mature adipocytes. When tested in rats or mice, phenelzine reduces food intake and/or fat accumulation without cardiac adverse effects. Novel amine oxidase inhibitors have been recently characterized in a quest for promising anti-inflammatory or anti-cancer approaches; however, their capacity to mitigate obesity has not been studied so far. Conclusions: The present review of the diverse effects of amine oxidase inhibitors impairing adipocyte differentiation or limiting excessive fat accumulation indicates that further studies are needed to reveal their potential anti-obesity properties.},
   author = {Christian Carpéné and Nathalie Boulet and Alice Chaplin and Josep Mercader},
   doi = {10.3390/MEDICINES6010009},
   issn = {2305-6320},
   issue = {1},
   journal = {Medicines (Basel, Switzerland)},
   keywords = {Christian Carpéné,Josep Mercader,MEDLINE,NCBI,NIH,NLM,Nathalie Boulet,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PMC6473341,PubMed Abstract,Review,doi:10.3390/medicines6010009,pmid:30650583},
   month = {1},
   pages = {9},
   pmid = {30650583},
   publisher = {Medicines (Basel)},
   title = {Past, Present and Future Anti-Obesity Effects of Flavin-Containing and/or Copper-Containing Amine Oxidase Inhibitors},
   volume = {6},
   url = {https://pubmed.ncbi.nlm.nih.gov/30650583/},
   year = {2019},
}
@article{Peng2016,
   abstract = {Given that the elevated serum semicarbazide-sensitive amine oxidase (SSAO) activity is associated with the severity of carotid atherosclerosis in clinic, the current study aims to investigate whether SSAO inactivation by semicarbazide is beneficial for established atherosclerotic lesions in LDLr knockout mice on a high-fat/high-cholesterol Western-type diet or after dietary lipid lowering. Despite no impact on plasma total cholesterol levels, the infiltration of circulating monocytes into peripheral tissues, and the size of atherosclerotic lesions, abrogation of SSAO activity resulted in the stabilization of established lesions as evidenced by the increased collagen contents under both conditions. Moreover, SSAO inactivation decreased Ly6Chighmonocytosis and lesion macrophage contents in hypercholesterolemic mice, while no effect was observed in mice after normalization of hypercholesterolemia by dietary lipid lowering. Strikingly, abrogation of SSAO activity significantly increased not only the absolute numbers of smooth muscle cells (SMCs), but also the percent of SMCs with a synthetic phenotype in established lesions of mice regardless of plasma cholesterol levels. Overall, our data indicate that SSAO inactivation in vivo stabilizes the established plaques mainly via inducing the switch of SMCs from a contractile to a synthetic phenotype. Targeting SSAO activity thus may represent a potential treatment for patients with atherosclerosis.},
   author = {Ya Peng and Jun Wang and Miao Zhang and Panpan Niu and Mengya Yang and Yilin Yang and Ying Zhao},
   doi = {10.1371/JOURNAL.PONE.0152758},
   issn = {1932-6203},
   issue = {4},
   journal = {PloS one},
   keywords = {Amine Oxidase (Copper-Containing) / antagonists & inhibitors,Amine Oxidase (Copper-Containing) / genetics,Amine Oxidase (Copper-Containing) / metabolism*,Animals,Atherosclerosis / chemically induced,Atherosclerosis / enzymology*,Atherosclerosis / genetics,Atherosclerosis / pathology,Atherosclerotic / chemically induced,Atherosclerotic / enzymology*,Atherosclerotic / genetics,Atherosclerotic / pathology,Cell Adhesion Molecules / antagonists & inhibitors,Cell Adhesion Molecules / genetics,Cell Adhesion Molecules / metabolism*,Dietary Fats / adverse effects,Dietary Fats / pharmacology,Female,Jun Wang,Knockout,LDL / genetics,LDL / metabolism,MEDLINE,Macrophages / enzymology,Macrophages / pathology,Male,Mice,Monocytes / enzymology,Muscle,Myocytes,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,PMC4820117,Plaque,PubMed Abstract,Receptors,Research Support,Smooth,Smooth Muscle / enzymology*,Smooth Muscle / pathology,Vascular / enzymology*,Vascular / pathology,Ya Peng,Ying Zhao,doi:10.1371/journal.pone.0152758,pmid:27043821},
   month = {4},
   pmid = {27043821},
   publisher = {PLoS One},
   title = {Inactivation of Semicarbazide-Sensitive Amine Oxidase Stabilizes the Established Atherosclerotic Lesions via Inducing the Phenotypic Switch of Smooth Muscle Cells},
   volume = {11},
   url = {https://pubmed.ncbi.nlm.nih.gov/27043821/},
   year = {2016},
}
@article{Hernandez-Guillamon2010,
   abstract = {Background and purpose: Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme involved in recruitment of lymphocytes and neutrophils through its semicarbazide-sensitive amine oxidase (SSAO) activity. We aimed to study plasma VAP-1/SSAO activity in relation to the risk for intracranial bleeding complications in patients with stroke treated with tissue plasminogen activator (tPA), the greatest safety concern with this treatment. Methods: In 141 patients with ischemic stroke, we measured VAP-1/SSAO activity in plasma taken before tPA administration. Hemorrhagic events were classified according to brain CT criteria and functional outcomes evaluated using the National Institutes of Health Stroke Scale. We also assessed the potential therapeutic effect of blocking VAP-1/SSAO activity in a rat embolic stroke model treated with tPA. Results: We saw significantly higher levels of plasma VAP-1/SSAO activity in patients who subsequently experienced hemorrhagic transformation. Elevated plasma VAP-1/SSAO activity also predicted worse neurological outcome in these patients. In the rat model, we confirmed that use of the inhibitor semicarbazide prevented adverse effects caused by delayed tPA administration, leading to a smaller infarct volume. Conclusions: Our data demonstrate that baseline VAP-1/SSAO activity predicts parenchymal hemorrhage after tPA, suggesting the safety of thrombolytic agents could be improved by considering VAP-1/SSAO activity. Furthermore, anti-VAP-1/SSAO drugs given with tPA may prevent neurological worsening in patients with ischemic stroke. Copyright © 2010 American Heart Association. All rights reserved.},
   author = {Mar Hernandez-Guillamon and Lidia Garcia-Bonilla and Montse Solé and Victoria Sosti and Mireia Parés and Mireia Campos and Arantxa Ortega-Aznar and Carmen Domínguez and Marta Rubiera and Marc Ribó and Manolo Quintana and Carlos A. Molina and José Alvarez-Sabín and Anna Rosell and Mercedes Unzeta and Joan Montaner},
   doi = {10.1161/STROKEAHA.110.584623},
   issn = {1524-4628},
   issue = {7},
   journal = {Stroke},
   keywords = {80 and over,Aged,Amine Oxidase (Copper-Containing) / blood*,Animals,Biomarkers / blood,Cell Adhesion Molecules / blood*,Comparative Study,Enzyme Activation / drug effects,Enzyme Activation / physiology,Female,Humans,Intracranial Hemorrhages / drug therapy,Intracranial Hemorrhages / enzymology*,Intracranial Hemorrhages / etiology,Joan Montaner,Lidia Garcia-Bonilla,MEDLINE,Male,Mar Hernandez-Guillamon,Middle Aged,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Nervous System Diseases / drug therapy,Nervous System Diseases / enzymology*,Nervous System Diseases / etiology,Predictive Value of Tests,Prospective Studies,PubMed Abstract,Rats,Sprague-Dawley,Stroke / complications,Stroke / drug therapy,Stroke / enzymology*,Tissue Plasminogen Activator / adverse effects*,Treatment Outcome,doi:10.1161/STROKEAHA.110.584623,pmid:20538694},
   pages = {1528-1535},
   pmid = {20538694},
   publisher = {Stroke},
   title = {Plasma VAP-1/SSAO activity predicts intracranial hemorrhages and adverse neurological outcome after tissue plasminogen activator treatment in stroke},
   volume = {41},
   url = {https://pubmed.ncbi.nlm.nih.gov/20538694/},
   year = {2010},
}
@article{Zhang2016,
   abstract = {Background and aims: Clinical studies have demonstrated that serum semicarbazide-sensitive amine oxidase (SSAO) activities positively correlate with the progression of atherosclerosis. The aim of the present study is to investigate the effect of SSAO inactivation on the development of atherosclerosis. Methods: Female LDLr knockout (KO) mice were given the Western-type diet for 6 and 9 weeks to induce the formation of early and advanced lesions, and semicarbazide (SCZ, 0.125%) was added into the drinking water to inactivate SSAO in vivo. Results: Despite no impact on plasma total cholesterol levels, abrogation of SSAO by SCZ not only resulted in the enlargement of both early (1.5-fold, p = 0.0043) and advanced (1.8-fold, p = 0.0013) atherosclerotic lesions, but also led to reduced/increased lesion contents of macrophages/smooth muscle cells (SMCs) (macrophage: ∼0.74-fold, p = 0.0002(early)/0.0016(advanced); SMC: ∼1.55-fold, p = 0.0003(early)/0.0001(advanced)), respectively. Moreover, SSAO inactivation inhibited the migration of circulating monocytes into peripheral tissues and reduced the amount of circulating Ly6Chigh monocytes (0.7-fold, p = 0.0001), which may account for the reduced macrophage content in lesions. In contrast, the increased number of SMCs in lesions of SCZ-treated mice is attributed to an augmented synthetic vascular SMC phenotype switch as evidenced by the increased proliferation of SMCs and accumulation of collagens in vivo. Conclusion: SSAO inactivation by SCZ promotes the phenotypic switch of SMCs and the development of atherosclerosis. The enzymatic activity of SSAO may thus represent a potential target in the prevention and/or treatment of atherosclerosis.},
   author = {Miao Zhang and Limin Liu and Feng Zhi and Panpan Niu and Mengya Yang and Xuemei Zhu and Ying Diao and Yanmei Li and Jun Wang and Ying Zhao},
   doi = {10.1016/J.ATHEROSCLEROSIS.2016.03.039},
   issn = {1879-1484},
   journal = {Atherosclerosis},
   keywords = {Amine Oxidase (Copper-Containing) / antagonists & inhibitors*,Animal,Animals,Antigens,Atherosclerosis / blood,Atherosclerosis / chemically induced*,Cholesterol / blood,Disease Models,Enzyme Inhibitors / pharmacology,Female,Inbred C57BL,Knockout,Limin Liu,Ly / metabolism,MEDLINE,Macrophages / metabolism,Miao Zhang,Mice,Monocytes / metabolism,Myocytes,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,Phenotype,PubMed Abstract,Research Support,Semicarbazides / pharmacology*,Smooth Muscle / drug effects*,Ying Zhao,doi:10.1016/j.atherosclerosis.2016.03.039,pmid:27065245},
   month = {6},
   pages = {76-82},
   pmid = {27065245},
   publisher = {Atherosclerosis},
   title = {Inactivation of semicarbazide-sensitive amine oxidase induces the phenotypic switch of smooth muscle cells and aggravates the development of atherosclerotic lesions},
   volume = {249},
   url = {https://pubmed.ncbi.nlm.nih.gov/27065245/},
   year = {2016},
}
@article{Reddy2024,
   abstract = {Caffeine is the world's most popular stimulant and psychoactive substance. Given the ubiquitous use of caffeine, it is crucial for us to comprehend how our body interacts with caffeine. The pharmacokinetics of caffeine and its action mechanisms have been reviewed in this paper. The safety and recommended dosage of caffeine in healthy adults and vulnerable populations like children and pregnant women are also discussed in this paper. While caffeine consumption is generally safe, this review paper also examines the potential effects that caffeine could have on human health and development. Studies indicated that caffeine exhibits neuroprotective properties, potentially serving as a preventive measure against the onset of neurodegenerative conditions such as Alzheimer's and Parkinson's disease. The article also explores various physiological effects of caffeine on the body, in addition to investigating novel drug delivery techniques, particularly nano-delivery systems designed to efficiently administer caffeine.},
   author = {Vundrala Sumedha Reddy and S. Shiva and Srinidhi Manikantan and Seeram Ramakrishna},
   doi = {10.1016/J.EJMCR.2024.100138},
   issn = {2772-4174},
   journal = {European Journal of Medicinal Chemistry Reports},
   keywords = {Caffeine,Drug delivery,Mechanism,Pharmacokinetics,Pharmacological effects,Pregnancy},
   month = {4},
   pages = {100138},
   publisher = {Elsevier Masson},
   title = {Pharmacology of caffeine and its effects on the human body},
   volume = {10},
   year = {2024},
}
@article{Marin2019,
   abstract = {Global obesity rates have reached pandemic proportions, increasing the risk of metabolic complications for hundreds of millions of individuals worldwide. Gaining insight on adipose tissue biology and understanding how fat pads behave during obesity is critical to investigate metabolic syndromes. Elucidation of cellular signaling pathways engaged by adipose tissue both in health and disease requires standardized protocols for protein extraction that yield consistently pure samples. A recurrent problem of currently available protocols is lipid or detergent contamination in extracted protein samples, which renders protein quantification inaccurate and, as a consequence, consistency and reproducibility of protein loading become unreliable. To overcome this problem, we improved the process of adipose tissue protein extraction by improving tissue lysis and decreasing lipid contamination. Here we describe the Removal of Excess Lipids (RELi) protocol to obtain increased yields of total proteins extracted from adipose tissue. The RELi protocol allows accurate and reproducible adipose tissue sample preparation for Western blot analysis and other investigative techniques requiring adipose tissue-derived proteins.},
   author = {R. Diaz Marin and S. Crespo-Garcia and Ariel Molly Wilson and P. Sapieha},
   doi = {10.1016/J.MEX.2019.04.010},
   issn = {2215-0161},
   journal = {MethodsX},
   keywords = {Adipose tissue,BAT,Protein extraction,Removal of excess lipids (RELi) protocol for protein extraction from white, brown and beige adipose,WAT,Western blot},
   month = {1},
   pages = {918-928},
   publisher = {Elsevier},
   title = {RELi protocol: Optimization for protein extraction from white, brown and beige adipose tissues},
   volume = {6},
   year = {2019},
}
@article{An2020,
   abstract = {As obesity becomes a global epidemic, the metabolism research field is increasingly focusing on studying the physiological and pathological roles of adipose tissues (AT). However, extracting proteins from AT is challenging due to abundant fat content of intracellular lipid droplets. Several commercial kits for extraction of AT proteins are available, as are protocols (such as the RELi protocol as well as other protein precipitation protocols). The protocols have been introduced to improve the quality and yield of extractions, but these methods either increase the cost or involve multiple steps. Herein, we describe a detailed protocol for mouse AT protein extractions based on our daily laboratory practice. This protocol requires only very common reagents and instruments, and can be completed in 90-120 min and provides good recovery of total protein content. Thus, this protocol is an economically attractive, time-saving and efficient way to extract proteins from the AT.},
   author = {Yu A. An and Philipp E. Scherer},
   doi = {10.21769/BIOPROTOC.3631},
   issn = {2331-8325},
   issue = {11},
   journal = {Bio-protocol},
   keywords = {MEDLINE,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PMC7842653,Philipp E Scherer,PubMed Abstract,Yu A An,doi:10.21769/BioProtoc.3631,pmid:33659303},
   month = {6},
   pmid = {33659303},
   publisher = {Bio Protoc},
   title = {Mouse Adipose Tissue Protein Extraction},
   volume = {10},
   url = {https://pubmed.ncbi.nlm.nih.gov/33659303/},
   year = {2020},
}
@article{Dezse2020,
   abstract = {It is well known among plastinators that acetone is a good degreaser when used at room temperature. In fact, the dehydration process is achieved by using acetone at-25º C, followed by a degreasing process utilizing acetone or dichloromethane at room temperature. The objective of this study was to identify the rate and effectiveness that cold acetone (-25º C) has on fat removal during the dehydration process and to compare it with the defatting phase at room temperature. Samples were soaked in-25º C acetone for 21 days (3 baths of 100% acetone) and then 20º C for 21 days (3 baths of 100% acetone). Acetone was changed at 7-day intervals and the “Dirty”/used acetone was collected and total fat content was determined using a rotary evaporator. Over a 42-day period, the samples demonstrated a uniform pattern of decreasing fat extraction during dehydration. However, when degreasing was initiated, a sharp increase of extraction was observed which ended with a steep decline. These findings were supported by mirrored purity readings with an acetonometer. Rate of extraction was greatest during the first seven days of both phases. Dehydration yielded 17.9 % more fat extracted by weight when compared to the defatting phase. This study represents the first report that the dehydration phase may play a more important role in degreasing than the defatting phase itself. Using acetone purity readings with calculated k-values for average rate of extraction data points allows one to quantify and determine a “successful extraction of fat.”.},
   author = {K. E. Dezse and W. P. Frank and C. A.C. Baptista},
   doi = {10.56507/MBJO3692},
   issn = {2311777X},
   issue = {1},
   journal = {Journal of Plastination},
   keywords = {Defatting,Degreasing,Dehydration,Fat,Plastination,Rotary evaporator},
   pages = {26-30},
   publisher = {International Society for Plastination},
   title = {Fat removal during acetone dehydration and defatting phases of plastination},
   volume = {32},
   year = {2020},
}
@article{Noble2009,
   abstract = {The measurement of protein concentration in an aqueous sample is an important assay in biochemistry research and development labs for applications ranging from enzymatic studies to providing data for biopharmaceutical lot release. Spectrophotometric protein quantitation assays are methods that use UV and visible spectroscopy to rapidly determine the concentration of protein, relative to a standard, or using an assigned extinction coefficient. Methods are described to provide information on how to analyze protein concentration using UV protein spectroscopy measurements, traditional dye-based absorbance measurements; BCA, Lowry, and Bradford assays and the fluorescent dye-based assays; amine derivatization and detergent partition assays. The observation that no single assay dominates the market is due to specific limitations of certain methods that investigators need to consider before selecting the most appropriate assay for their sample. Many of the dye-based assays have unique chemical mechanisms that are prone to interference from chemicals prevalent in many biological buffer preparations. A discussion of which assays are prone to interference and the selection of alternative methods is included. © 2009 Elsevier Inc. All rights reserved.},
   author = {James E. Noble and Marc J.A. Bailey},
   doi = {10.1016/S0076-6879(09)63008-1},
   issn = {0076-6879},
   issue = {C},
   journal = {Methods in Enzymology},
   month = {1},
   pages = {73-95},
   pmid = {19892168},
   publisher = {Academic Press},
   title = {Chapter 8 Quantitation of Protein},
   volume = {463},
   year = {2009},
}
@article{Cai2022,
   abstract = {Glycolysis is the predominant energy-yielding metabolic pathway in most cancer cells and rapidly proliferating cells. Currently available methods for glycolysis rate analysis are either time-consuming or cost-intensive/specialized equipment-dependent. The present study demonstrates a convenient, fast, and low-cost enzyme-coupled fluorometric assay for rapid quantification of glycolysis rate in small amount of cells. This assay involves the oxidation of cell-secreted lactate to produce hydrogen peroxide (H2O2) and subsequent conversion of Amplex Red (10-acetyl-3,7-dihydroxyphenoxazine) to fluorometric resorufin, in the presence of lactate oxidase (LOx) and peroxidase. High detection sensitivity and stability were realized by optimization of assay medium composition, enzyme and substrate concentration, and assay procedure. The lower limit of detection on HeLa cells was achieved on 50 cells per sample and the optimized linear range of the detection was 250–7000 cells per sample (r2 = 0.9842). The repetitive intraday and interday measurements of HeLa cell provided small variance and were highly agreeable with the results of endpoint method, which is a conventional validated method but detects lactate in relatively long time of larger cell population. The present assay was successfully applied on measuring the glycolytic parameters of human cancer cells (HeLa, HepG2) and mouse immune cells (T cells, macrophages), indicating great potential for wide application in cancerous and immunological research. Graphical abstract: [Figure not available: see fulltext.]},
   author = {Limeng Cai and Yuqi Wang and Ying Yang and Hao Wu},
   doi = {10.1007/S00216-021-03834-2/METRICS},
   issn = {16182650},
   issue = {5},
   journal = {Analytical and Bioanalytical Chemistry},
   keywords = {96-Well microplate,Enzyme-coupled assay,Fluorometric assay,Glycolysis rate,Lactate},
   month = {2},
   pages = {1987-1997},
   pmid = {34984508},
   publisher = {Springer Science and Business Media Deutschland GmbH},
   title = {A low-cost, enzyme-coupled fluorescent assay for rapid quantification of glycolysis rate of cells},
   volume = {414},
   url = {https://link.springer.com/article/10.1007/s00216-021-03834-2},
   year = {2022},
}
@article{Karakuzu2019,
   abstract = {Reagents such as Amplex® Red have been developed for detecting hydrogen peroxide (H2O2) and are used to measure the release of H2O2 from biological samples such as mammalian leukocytes undergoing the oxidative burst. Caenorhabditis elegans is commonly used as a model host in the study of interactions with microbial pathogens and releases reactive oxygen species (ROS) as a component of its defense response. We adapted the Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit to measure H2O2 output from live Caenorhabditis elegans exposed to microbial pathogens. The assay differs from other forms of ROS detection in the worm, like dihydrofluorescein dyes and genetically encoded probes such as HyPer, in that it generally detects released, extracellular ROS rather than intracellular ROS, though the distinction between the two is blurred by the fact that certain species of ROS, including H2O2, can cross membranes. The protocol involves feeding C. elegans on a lawn of the pathogen of interest for a period of time. The animals are then rinsed off the plates in buffer and washed to remove any microbes on their cuticle. Finally, the animals in buffer are distributed into 96-well plates and Amplex® Red and horseradish peroxidase (HRP) are added. Any H2O2 released into the buffer by the worms will react with the Amplex® Red reagent in a 1:1 ratio in the presence of HRP to produce the red fluorescent excitation product resorufin that can be measured fluorometrically or spectrophotometrically, and the amount of H2O2 released can be calculated by comparison to a standard curve. The assay is most appropriate for studies focused on released ROS, and its advantages include ease of use, the ability to use small numbers of animals in a plate reader assay in which measurements can be taken either fluorometrically or spectrophotometrically.},
   author = {Ozgur Karakuzu and Melissa R. Cruz and Yi Liu and Danielle A. Garsin},
   doi = {10.21769/BIOPROTOC.3409},
   issn = {2331-8325},
   issue = {21},
   journal = {Bio-protocol},
   keywords = {Danielle A Garsin,MEDLINE,Melissa R Cruz,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Ozgur Karakuzu,PMC7375442,PubMed Abstract,doi:10.21769/BioProtoc.3409,pmid:32699812},
   month = {11},
   pmid = {32699812},
   publisher = {Bio Protoc},
   title = {Amplex Red Assay for Measuring Hydrogen Peroxide Production from Caenorhabditis elegans},
   volume = {9},
   url = {https://pubmed.ncbi.nlm.nih.gov/32699812/},
   year = {2019},
}
@article{Bour2009,
   abstract = {Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-monthold AOC3-KO males than in age-matched wild-type controls. However, WAT from AOC3-KO mice contained lower CD45 mRNA levels and fewer CD45+ leukocytes. Subpopulation analyses revealed a diminished infiltration of WAT by T cells, macrophages, natural killer, and natural killer T cells. A decrease in leukocyte content in WAT was also detected in female AOC3-KO mice as early as 2 months of age, whereas increased fat mass was evident by 6 months of age. Reduced CD45+ populations in WAT of AOC3-KO mice was not rescued by human SSAO/VAP-1 expression on adipocytes under the control of aP2, suggesting the importance of vascular AOC3 in leukocyte entrance into fat. Our results indicate that SSAO/VAP-1 is instrumental for the presence of leukocytes in WAT. Therefore, AOC3-KO mice present a unique model of mild obesity, characterized by increased WAT devoid of low-grade inflammation. Copyright © American Society for Investigative Pathology.},
   author = {Sandy Bour and Sylvie Caspar-Bauguil and Zsuzsa Iffiú-Soltész and Maryse Nibbelink and Béatrice Cousin and Mari Miiluniemi and Marko Salmi and Craig Stolen and Sirpa Jalkanen and Louis Casteilla and Luc Pénicaud and Philippe Valet and Christian Carpéné},
   doi = {10.2353/AJPATH.2009.080612},
   issn = {1525-2191},
   issue = {3},
   journal = {The American journal of pathology},
   keywords = {Adipose Tissue / pathology,Adipose Tissue / physiology*,Amine Oxidase (Copper-Containing) / deficiency*,Amine Oxidase (Copper-Containing) / genetics*,Animals,Cell Adhesion Molecules / deficiency*,Cell Adhesion Molecules / genetics*,Christian Carpéné,Flow Cytometry,Humans,Inbred C57BL,Knockout,Leukocytes / physiology*,MEDLINE,Mice,Monoamine Oxidase / deficiency*,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Obesity / genetics,PMC2665766,PubMed Abstract,Sandy Bour,Semicarbazides / pharmacology*,Sylvie Caspar-Bauguil,Transgenic,doi:10.2353/ajpath.2009.080612,pmid:19218346},
   pages = {1075-1083},
   pmid = {19218346},
   publisher = {Am J Pathol},
   title = {Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition},
   volume = {174},
   url = {https://pubmed.ncbi.nlm.nih.gov/19218346/},
   year = {2009},
}
@article{Lyles1996,
   abstract = {Mammalian plasma and tissues contain various soluble and membrane-bound enzymes which metabolize the synthetic amine benzylamine particularly well. The sensitivity of these enzymes to inhibition by semicarbazide and related compounds suggests that they contain a cofactor with a reactive carbonyl group, which has been proposed to be either pyridoxal phosphate, pyrroloquinoline quinone or (more recently) 6-hydroxydopa. It is not yet clear if all of these semicarbazide-sensitive amine oxidases (SSAOs) are copper-dependent enzymes. A variety of compounds have now been identified as relatively selective inhibitors to distinguish the SSAOs from other amine oxidases, in order to investigate the properties of SSAOs and their potential role in biogenic and xenobiotic amine metabolism in vivo. While plasma SSAO is soluble, most tissue SSAOs appear to be membrane-bound, probably plasmalemmal enzymes, which may be capable of metabolizing extracellular amines. Vascular (and non-vascular) smooth muscle cells have particularly high SSAO activity, although recently the enzyme has been found in other cell types (e.g. adipocytes, chondrocytes, odontoblasts) implying a functional importance not restricted solely to smooth muscle. The substrate specificity of plasma and tissue SSAOs shows considerable species-related variations. For example, while some endogenously-occurring aromatic amines such as tyramine and tryptamine are metabolized well by SSAO in homogenates of rat blood vessels, and also in vitro inhibition of SSAO can potentiate vasoconstrictor actions of these amines in rat vascular preparations, these amines are poor substrates for human SSAO, thus complicating attempts to generalize possible physiological roles for these enzymes. Vascular SSAO can metabolize the xenobiotic aliphatic amine, allylamine, to the cytotoxic aldehyde acrolein and this has been linked to the ability of allylamine administration to produce cardiovascular lesions in experimental animals, sometimes mimicking features of atherosclerotic disease. Recent studies showing that the endogenously-occurring aliphatic amines methylamine and aminoacetone are metabolized in vitro to formaldehyde and methylglyoxal, respectively, by SSAO in some animal (including human) tissues, suggest the possibility that toxicological consequences upon cellular function could result if such conversions occur in vivo.},
   author = {G. A. Lyles},
   doi = {10.1016/1357-2725(95)00130-1},
   issn = {13572725},
   issue = {3},
   journal = {International Journal of Biochemistry and Cell Biology},
   keywords = {amine oxidase inhibitors,aromatic and aliphatic amine metabolism,blood plasma,cytotoxicity,semicarbazide-sensitive amine oxidase,vascular smooth muscle},
   pages = {259-274},
   pmid = {8920635},
   publisher = {Elsevier Ltd},
   title = {Mammalian plasma and tissue-bound semicarbazide-sensitive amine oxidases: Biochemical, pharmacological and toxicological aspects},
   volume = {28},
   year = {1996},
}
@article{Visentin2005,
   abstract = {A soluble form of semicarbazide-sensitive amine oxidase (SSAO) circulating in plasma is known to increase in type 1 and 2 diabetes. This cuproenzyme generates hydrogen peroxide, ammonia, and aldehydes when oxidizing circulating biogenic or exogenous amines. Based on the angiotoxicity of these products, inhibition of SSAO has been proposed to prevent vascular complications of diabetes. However, substrates of SSAO and monoamine oxidase (MAO) have been recently evidenced to activate glucose utilisation in insulin-sensitive tissues and to exhibit antihyperglycemic actions. To determine whether amine oxidase blockade or activation could be beneficial for diabetes, we aimed at comparing the influence of prolonged treatments with semicarbazide (SSAO-inhibitor), pargyline (MAO-inhibitor), or tyramine (amine oxidase substrate) on amine oxidase activities and glycemic control in streptozotocin-induced diabetic rats. The increase in plasma SSAO was confirmed in diabetic rats, while MAO and SSAO were decreased in subcutaneous adipose tissue when compared with normoglycemic controls. Among the diabetic rats, only those receiving tyramine exhibited slightly decreased hyperglycemia and improved glucose tolerance. Adipocytes from untreated or treated diabetic rats shared similar sensitivity to insulin. However glucose uptake activation and lipolysis inhibition in response to amine oxidase substrates combined with vanadate were impaired in rats treated with amine oxidase inhibitors. Thus, amine oxidase inhibition does not improve metabolic control while prolonged administration of tyramine slightly improves glucose disposal. It is therefore concluded that amine oxidase activation by increased substrate supply elicits insulin-like actions that may be more beneficial in diabetes than SSAO inhibition formerly proposed to prevent vascular complications. © 2005 Elsevier B.V. All rights reserved.},
   author = {Virgile Visentin and Sandy Bour and Jérémie Boucher and Danielle Prévot and Philippe Valet and Catherine Ordener and Angelo Parini and Christian Carpéné},
   doi = {10.1016/j.ejphar.2005.08.051},
   issn = {00142999},
   issue = {1-3},
   journal = {European Journal of Pharmacology},
   keywords = {Adipose tissue,Diabetes,Insulin,Monoamine oxidase,SSAO (Semicarbazide-sensitive amine oxidase)},
   month = {10},
   pages = {139-146},
   pmid = {16202994},
   title = {Glucose handling in streptozotocin-induced diabetic rats is improved by tyramine but not by the amine oxidase inhibitor semicarbazide},
   volume = {522},
   year = {2005},
}
@article{Stolen2004,
   abstract = {Semicarbazide-sensitive amine oxidases (SSAO) are copper-containing enzymes that oxidatively deaminate primary amines to produce hydrogen peroxide, ammonium, and specific aldehydes. Vascular adhesion protein-1 (VAP-1) is a cell surface and soluble molecule that possesses SSAO activity. VAP-1 protein, SSAO activity, and SSAO reaction products are elevated in the serum of patients with diabetes, congestive heart failure, and specific inflammatory liver diseases. By expressing human VAP-1/SSAO on mouse endothelial cells and subsequently in the serum, and by chronically treating the transgenic mice for 15 months with a high-fat diet and a physiological substrate for SSAO, methylamine, the in vivo roles of SSAO were assessed. The VAP-1 transgene increased the mouse body mass index and subcutaneous abdominal fat pad weights in a manner independent of food consumption. The transgene together with increased SSAO substrate availability enhanced glucose uptake in an SSAO-dependent manner. The increased SSAO activity also led to diabetes-like complications, including advanced glycation end product formation, elevated blood pressure, altered atherosclerosis progression, and nephropathy. These findings suggest that, although manipulation of VAP-1/SSAO has potential to serve as a therapeutic treatment in insulin-resistant conditions, care must be taken to fully understand its impact on obesity and vascular damage.},
   author = {Craig M. Stolen and Rami Madanat and Luc Marti and Seppo Kari and Gennady G. Yegutkin and Hannu Sariola and Antonio Zorzano and Sirpa Jalkanen},
   doi = {10.1096/fj.03-0562fje},
   issn = {15306860},
   issue = {6},
   journal = {The FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
   pages = {702-704},
   pmid = {14977883},
   title = {Semicarbazide sensitive amine oxidase overexpression has dual consequences: insulin mimicry and diabetes-like complications.},
   volume = {18},
   year = {2004},
}
@article{Bonaiuto2010,
   abstract = {Kinetic studies were performed with various alkanamines as " substrate probes" of the properties of the active site of the human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1). We found that the enzyme-substrate recognition step is mainly controlled by apolar interactions and that a " good" substrate has a molecular structure containing a long aliphatic chain and a second positive charge at a distance greater than 12 from the reactive amino group. In this context, we identified a novel substrate for the human SSAO/VAP-1, 1,12-diaminododecane (DIADO), which is characterised by the highest catalytic efficiency reported to date in comparison to the prototypic substrate benzylamine. Computational docking studies revealed the structural basis of this behaviour, highlighting the key role played by Lys393 in hindering substrate docking. Maximum SSAO/VAP-1 activity is reached at relatively low concentrations of DIADO (10-30 μM), and, in these conditions, it has good selectivity: it is a good substrate of SSAO/VAP-1 but not of human adipocyte monoamine oxidases or pig kidney diamine oxidase. From these findings, it appears that DIADO can be used as a new substrate for human SSAO/VAP-1 to elicit glucose transport into adipocytes, and may consequently have potential pharmacological applications in the design of anti-diabetic agents. © 2010 Elsevier Masson SAS.},
   author = {Emanuela Bonaiuto and Michele Lunelli and Marina Scarpa and Roberto Vettor and Gabriella Milan and Maria Luisa Di Paolo},
   doi = {10.1016/j.biochi.2010.03.006},
   issn = {03009084},
   issue = {7},
   journal = {Biochimie},
   keywords = {Computational docking,PH dependence,SSAO/VAP-1 substrates,Semicarbazide-sensitive amine oxidases,Structure-function relationships},
   month = {7},
   pages = {858-868},
   pmid = {20298739},
   title = {A structure-activity study to identify novel and efficient substrates of the human semicarbazide-sensitive amine oxidase/VAP-1 enzyme},
   volume = {92},
   year = {2010},
}
@article{Dunkel2008,
   abstract = {SSAO/VAP-1 is not only involved in the metabolism of biogenic and xenobiotic primary amines and in the production of metabolites with cytotoxic effects or certain physiological actions, but also plays a role, for example, as an adhesion molecule, in leukocyte trafficking, in regulating glucose uptake and in adipocyte homeostasis. Interest in the enzyme has been stimulated by the findings that the activities of the SSAOs are altered (mostly increased) in various human disorders, including diabetes, congestive heart failure, liver cirrhosis, Alzheimer's disease and several inflammatory diseases, although the underlying causes are often unknown. On the basis of their insulin-mimicking effect, SSAO substrates are possibly capable of ameliorating metabolic changes in diabetes, while SSAO inhibitors (somewhat of a contradiction) are of potential benefit in preventing diabetes complications, atherosclerosis and oxidative stress contributing to several disorders or modulating inflammation, and hence may be of substantial therapeutic value. Great efforts have been made to develop novel compounds which may lead to future drugs useful in therapy, based on their effects on SSAO/VAP-1, and some of the results relating to novel substrates and inhibitors are surveyed in the present review. © 2008 Bentham Science Publishers Ltd.},
   author = {P. Dunkel and A. Gelain and D. Barlocco and N. Haider and K. Gyires and B. Sperlagh and K. Magyar and E. Maccioni and A. Fadda and P. Matyus},
   doi = {10.2174/092986708785133022},
   issn = {0929-8673},
   issue = {18},
   journal = {Current medicinal chemistry},
   keywords = {A Gelain,Alzheimer Disease / drug therapy,Amine Oxidase (Copper-Containing) / antagonists & inhibitors*,Amine Oxidase (Copper-Containing) / chemistry*,Amine Oxidase (Copper-Containing) / metabolism,Amines / chemistry,Animals,Blood / metabolism,Cattle,Cell Adhesion Molecules / metabolism,Diabetes Mellitus / drug therapy,Humans,Inhibitory Concentration 50,MEDLINE,Monoamine Oxidase / chemistry*,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,Non-U.S. Gov't,P Dunkel,P Mátyus,Plasma / metabolism,PubMed Abstract,Rats,Research Support,Review,Semicarbazides / chemistry*,Substrate Specificity,doi:10.2174/092986708785133022,pmid:18691041},
   month = {7},
   pages = {1827-1839},
   pmid = {18691041},
   publisher = {Curr Med Chem},
   title = {Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1: recent developments concerning substrates and inhibitors of a promising therapeutic target},
   volume = {15},
   url = {https://pubmed.ncbi.nlm.nih.gov/18691041/},
   year = {2008},
}
@article{Stevanato2011,
   abstract = {Kinetic measurements of a novel copper-dependent amine oxidase, purified from rat liver mitochondria matrix, were carried out using various substrates in a large pH (5.6-10.2) and ionic strength range (5-200 mM), in order to study the docking of substrates to the enzyme and, as a consequence, to verify the physicochemical characteristics of the active site. Relatively small changes of V max values (approx. 2.5-folds) over the substrates tested, suggest that the rate determining step of the catalysis is only slightly affected by amine chemical structure. In contrast, the strong change of K M and k c/K M values (approx. two orders of magnitude) indicates electrostatic control of the docking process, since the changes of K M and k c/K M values appear due to the presence of positively charged groups in the substrate molecules. These results suggest the presence in the enzyme active site of two negatively charged amino acid residues which seem to interact with positively charged groups of the substrate molecules. Analogies and differences with bovine serum amine oxidase are also described. © 2010 Springer-Verlag.},
   author = {Roberto Stevanato and Sara Cardillo and Michele Braga and Angela De Iuliis and Valentina Battaglia and Antonio Toninello and Enzo Agostinelli and Fabio Vianello},
   doi = {10.1007/S00726-010-0708-Y},
   issn = {1438-2199},
   issue = {2},
   journal = {Amino acids},
   keywords = {Amine Oxidase (Copper-Containing) / chemistry*,Amine Oxidase (Copper-Containing) / metabolism,Animals,Cattle,Enzyme Stability,Fabio Vianello,Hydrogen-Ion Concentration,Kinetics,Liver / chemistry,Liver / enzymology*,MEDLINE,Mitochondria,NCBI,NIH,NLM,National Center for Biotechnology Information,National Institutes of Health,National Library of Medicine,PubMed Abstract,Rats,Roberto Stevanato,Sara Cardillo,Substrate Specificity,doi:10.1007/s00726-010-0708-y,pmid:20686801},
   pages = {713-720},
   pmid = {20686801},
   publisher = {Amino Acids},
   title = {Preliminary kinetic characterization of a copper amine oxidase from rat liver mitochondria matrix},
   volume = {40},
   url = {https://pubmed.ncbi.nlm.nih.gov/20686801/},
   year = {2011},
}
@article{Yraola2007,
   abstract = {A new vanadium salt, hexakis(benzylammonium) decavanadate (V) dihydrate (C7NH10)6(V10O28) ·2H2O (1), has been synthesized as well as characterized chemically and biologically. An in vitro enzyme assay revealed that compound 1 is oxidized to the same extent as a combination of benzylamine and vanadate by the enzyme semicarbazide-sensitive amine oxidase (SSAO), and therefore can be considered an SSAO substrate. It also stimulates glucose uptake in isolated rat adipocytes in a dose-dependent manner. We describe here the results of 51V-NMR experiments that, combined with the in vitro results, corroborate that compound 1 could act as a prodrug of di-peroxovanadate ([V(OH)2(OO)2(OH)2]2-) insulin mimetics. © 2007 The Authors.},
   author = {Francesc Yraola and Silvia García-Vicente and Luc Marti and Fernando Albericio and Antonio Zorzano and Miriam Royo},
   doi = {10.1111/J.1747-0285.2007.00516.X},
   issn = {1747-0285},
   issue = {6},
   journal = {Chemical Biology & Drug Design},
   keywords = {benzylamine vanadate,diabetes,insulin mimetic,prodrug design},
   month = {6},
   pages = {423-428},
   pmid = {17581236},
   publisher = {John Wiley & Sons, Ltd},
   title = {Understanding the Mechanism of Action of the Novel SSAO Substrate (C7NH10)6(V10O28)·2H2O, a Prodrug of Peroxovanadate Insulin Mimetics},
   volume = {69},
   url = {https://onlinelibrary.wiley.com/doi/full/10.1111/j.1747-0285.2007.00516.x https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1747-0285.2007.00516.x https://onlinelibrary.wiley.com/doi/10.1111/j.1747-0285.2007.00516.x},
   year = {2007},
}
@article{Copeland.R.A.2005,
   author = {Copeland R. A.},
   edition = {46},
   journal = { Methods of biochemical analysis},
   pages = {1-265},
   publisher = { Methods of biochemical analysis},
   title = {Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists.},
   volume = {46},
   year = {2005},
}