{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T20:03:41Z","timestamp":1776974621401,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T00:00:00Z","timestamp":1677801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u00b5M vs. 65.35 \u00b5M). Aminoacetone- and methylamine-induced VSMCs death at concentrations of 50 &amp; 1000 \u00b5M, and their cytotoxic effect, was reversed with 100 \u00b5M 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 &lt; 0.0001), while \u03b2APN demonstrated inhibitory potential only in benzylamine-treated cells (* p &lt; 0.05). Treatment with benzylamine, methylamine and aminoacetone reduced the total GSH levels (**** p &lt; 0.0001); the addition of MDL72527 and \u03b2APN 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.<\/jats:p>","DOI":"10.3390\/ijms24054946","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T03:49:08Z","timestamp":1678074548000},"page":"4946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Impact of Semicarbazide Sensitive Amine Oxidase Activity on Rat Aortic Vascular Smooth Muscle Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Vesna","family":"Manasieva","sequence":"first","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, School of Medical Sciences, Imperial College, London SW7 2AZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shori","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A.","family":"Lione","sequence":"additional","affiliation":[{"name":"Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9701-2985","authenticated-orcid":false,"given":"Anwar R.","family":"Baydoun","sequence":"additional","affiliation":[{"name":"Faculty of Health and Life Sciences, School of Pharmacy, De Montford University, Leicester LE1 9BH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Skamarauskas","sequence":"additional","affiliation":[{"name":"Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00125-004-1346-2","article-title":"Adipocytes release a soluble form of VAP-1\/SSAO by a metalloprotease-dependent process and in a regulated manner","volume":"47","author":"Abella","year":"2004","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1161\/01.RES.0000134630.68877.2F","article-title":"Origins of Serum Semicarbazide-Sensitive Amine Oxidase","volume":"95","author":"Stolen","year":"2004","journal-title":"Circ. 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