{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:20:52Z","timestamp":1773249652162,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Abdominal aortic aneurysm (AAA) is a serious vascular disease for which there is no effective drug treatment. The incidence of AAA increases significantly as a subject ages, and the molecular mechanism of AAA formation remains elusive. In the present study, we investigated the role of syndecan\u20104 (SDC4), an important component of focal adhesions, in AAA formation and its association with phenotypic changes in vascular smooth muscle cells (VSMCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The protein expression levels of SDC4 were significantly decreased in human AAA tissue and those of an AAA mouse model. Moreover, SDC4 knockout (KO) in mice accelerated the formation and rupture of AAAs induced by angiotensin II (Ang II) and calcium chloride (CaCl<jats:sub>2<\/jats:sub>)<\/jats:p><jats:p>Mechanistically, the decrease in SDC4 led to the transformation of cultured VSMCs from a contractile to a secretory phenotype. The RhoA\u2010F\/G\u2010actin\u2010myocardin\u2010related transcription factor\u2010A (MRTF\u2010A) signalling pathway was shown to be involved in SDC4\u2010dependent VSMC alteration. Sphingosine\u20101\u2010phosphate (S1P), a G\u2010protein\u2010coupled receptor, attenuated the AAA formation in SDC4\u2010KO and wild\u2010type (WT) mice in response to Ang II and CaCl<jats:sub>2<\/jats:sub> stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We herein demonstrated that silencing SDC4 was associated with increased AAA formation and phenotypic changes in VSMCs via the RhoA\u2010F\/G\u2010actin\u2010MRTF\u2010A pathway. These findings indicated that a reduction in SDC4 expression was an important pathological alteration and potential therapeutic target for AAA formation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.605","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T12:15:19Z","timestamp":1640175319000},"source":"Crossref","is-referenced-by-count":13,"title":["A reduction in the vascular smooth muscle cell focal adhesion component syndecan\u20104 is associated with abdominal aortic aneurysm formation"],"prefix":"10.1002","volume":"11","author":[{"given":"Jiaxin","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School, MOE Key Laboratory of Model Animal for Disease Study, Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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