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Insufficient repair of these plaques leads to thrombosis and subsequent ACS. Central to this process is the modulation of vascular smooth muscle cells (VSMCs) phenotypes, emphasizing their pivotal role in atherosclerotic plaque stability and healing post\u2010disruption. Here, an expansion of FSP1<jats:sup>+<\/jats:sup> cells in a tandem stenosis (TS) model of atherosclerotic mice is unveiled, predominantly originating from VSMCs through single\u2010cell RNA sequencing (scRNA\u2010seq) analyses and VSMC lineage tracing studies. Further investigation identified TEA domain transcription factor 1 (TEAD1) as the key transcription factor driving the trans\u2010differentiation of VSMCs into fibroblast\u2010like cells. In vivo experiments using a TS model of plaque rupture demonstrated that TEAD1 played a crucial role in promoting plaque stability and healing post\u2010rupture through pharmacological or TEAD1\u2010AAV treatments. Mechanistically, it is found that TEAD1 promoted the expression of fibroblast markers through the Wnt4\/\u03b2\u2010Catenin pathway, facilitating the trans\u2010differentiation. Thus, this study illustrated that TEAD1 played a critical role in promoting the trans\u2010differentiation of VSMCs into fibroblast\u2010like cells and subsequent extracellular matrix production through the Wnt4\/\u03b2\u2010Catenin pathway. Consequently, this process enhanced the healing mechanisms following plaque rupture, elucidating potential therapeutic avenues for managing atherosclerotic instability.<\/jats:p>","DOI":"10.1002\/advs.202407408","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T05:47:05Z","timestamp":1733982425000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["TEAD1\u2010Mediated Trans\u2010Differentiation of Vascular Smooth Muscle Cells into Fibroblast\u2010Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques"],"prefix":"10.1002","volume":"12","author":[{"given":"Ming","family":"Zhai","sequence":"first","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yefei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixia","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology School of Medicine Xinhua Hospital Shanghai Jiaotong University  Shanghai 200092 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Feinberg","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Department of Medicine Brigham and Women's Hospital Harvard Medical School  Boston MA 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2937-0024","authenticated-orcid":false,"given":"Wenhui","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University  Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.08.012"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2022.3926"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00769-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2021.09.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy419"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.915126"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00687-9"},{"key":"e_1_2_9_8_1","first-page":"293","volume":"384","author":"Wang X.","year":"2021","journal-title":"N. 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