{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:32:40Z","timestamp":1784691160796,"version":"3.55.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Thoracic aortic aneurysms (TAAs) are abnormal aortic dilatations and a major cardiovascular complication of Marfan syndrome. We previously demonstrated a critical role for vascular smooth muscle (VSM) SirT1 (sirtuin-1), a lysine deacetylase, against maladaptive aortic remodeling associated with chronic oxidative stress and aberrant activation of MMPs (matrix metalloproteinases).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      In this study, we investigated whether redox dysregulation of SirT1 contributed to the pathogenesis of TAA using fibrillin-1 hypomorphic mice (Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                      ), an established model of Marfan syndrome prone to aortic dissection\/rupture.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Oxidative stress markers 3-nitrotyrosine and 4-hydroxynonenal were significantly elevated in aortas of patients with Marfan syndrome. Moreover, reversible oxidative post-translational modifications (rOPTM) of protein cysteines, particularly S-glutathionylation, were dramatically increased in aortas of Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                      mice, before induction of severe oxidative stress markers. Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                      aortas and VSM cells exhibited an increase in rOPTM of SirT1, coinciding with the upregulation of acetylated proteins, an index of decreased SirT1 activity, and increased MMP2\/9 activity. Mechanistically, we demonstrated that TGF\u03b2 (transforming growth factor beta), which was increased in Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                      aortas, stimulated rOPTM of SirT1, decreasing its deacetylase activity in VSM cells. VSM cell\u2013specific deletion of SirT1 in Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                      mice (SMKO-Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                      ) caused a dramatic increase in aortic MMP2 expression and worsened TAA progression, leading to aortic rupture in 50% of SMKO-Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                      mice, compared with 25% of Fbn1\n                      <jats:sup>mgR\/mgR<\/jats:sup>\n                      mice. rOPTM of SirT1, rOPTM-mediated inhibition of SirT1 activity, and increased MMP2\/9 activity were all exacerbated by the deletion of Glrx (glutaredoxin-1), a specific deglutathionylation enzyme, while being corrected by overexpression of Glrx or of an oxidation-resistant SirT1 mutant in VSM cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our novel findings strongly suggest a causal role of S-glutathionylation of SirT1 in the pathogenesis of TAA. Prevention or reversal of SirT1 rOPTM may be a novel therapeutic strategy to prevent TAA and TAA dissection\/ruptures in individuals with Marfan syndrome, for which, thus far, no targeted therapy has been developed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.123.319145","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T05:01:18Z","timestamp":1686200478000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome"],"prefix":"10.1161","volume":"43","author":[{"given":"Enkhjargal","family":"Budbazar","sequence":"first","affiliation":[{"name":"Vascular Biology Section (E.B., S.S.P.D.L., Y.T., H.L., Y.H., Y.W., P.M.S., X.Y., J.B.G., X.W., J.H., F.S.), Department of Medicine, Boston University Chobenian &amp; Avedisian School of Medicine, 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