{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:33Z","timestamp":1792787613854,"version":"4.5.0"},"reference-count":45,"publisher":"American Society for Clinical Investigation","issue":"5","funder":[{"name":"NIH","award":["5R01HL130113-02"],"award-info":[{"award-number":["5R01HL130113-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,8]]},"abstract":"<jats:p>\n                    Loss-of-function mutations in genes encoding contractile proteins have been observed in thoracic aortic aneurysms (TAA). To gain insight into the contribution of contractile protein deficiency in the pathogenesis of TAA, we examined human aneurysm samples. We found multiple contractile gene products deficient in TAA samples, and in particular, expression of SM22\u03b1 was inversely correlated with aneurysm size. SM22\u03b1-deficient mice demonstrated pregnancy-induced aortic dissection, and SM22\u03b1 deficiency worsened aortic aneurysm in\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>C1039G\/+<\/jats:sup>\n                    <\/jats:italic>\n                    (Marfan) mice, validating this gene product as a TAA effector. We found that repression of SM22\u03b1 was enforced by increased activity of the methyltransferase EZH2. TGF-\u03b2 effectors such as SMAD3 were excluded from binding SM22\u03b1-encoding chromatin (\n                    <jats:italic>TAGLN)<\/jats:italic>\n                    in TAA samples, while treatment with the EZH2 inhibitor GSK343 improved cytoskeletal architecture and restored SM22\u03b1 expression. Finally, inhibition of EZH2 improved aortic performance in\n                    <jats:italic>\n                      Fbn1\n                      <jats:sup>C1039G\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice, in association with restoration of contractile protein expression (including SM22\u03b1). Together, these data inform our understanding of contractile protein deficiency in TAA and support the pursuit of chromatin modifying factors as therapeutic targets in aortic disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.97493","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T11:02:53Z","timestamp":1520420573000},"source":"Crossref","is-referenced-by-count":46,"title":["Inhibition of the methyltranferase EZH2 improves aortic performance in experimental thoracic aortic aneurysm"],"prefix":"10.1172","volume":"3","author":[{"given":"Christian L.","family":"Lino Cardenas","sequence":"first","affiliation":[{"name":"Thoracic Aortic Center,"},{"name":"Cardiovascular Research Center,"},{"name":"Cardiology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chase W.","family":"Kessinger","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center,"},{"name":"Cardiology, Department 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