{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:50Z","timestamp":1785410570246,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","award":["2023xkj152"],"award-info":[{"award-number":["2023xkj152"]}],"id":[{"id":"10.13039\/501100002947","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2023xkj152"],"award-info":[{"award-number":["2023xkj152"]}],"id":[{"id":"https:\/\/ror.org\/03xb04968","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aortic dissection (AD) is a severe vascular condition marked by abrupt onset, rapid progression, and heightened mortality rates. Vascular smooth muscle cells (VSMCs), the predominant cellular component of the arterial media, are essential for maintaining the structural integrity and functionality of blood vessels. Recent studies have associated Cysteine-rich protein 2 (CSRP2) with the advancement of several vascular diseases. The involvement of CSRP2 in AD progression is unclear. Aortic tissues were collected from patients for RNA sequencing and histological analysis. A mouse model of AD was created using \u03b2-aminopropionitrile monofumarate (BAPN), while VSMC phenotypic switching was induced by platelet-derived growth factor BB (PDGF-BB). Adeno-associated virus vector was used to overexpress CSRP2 in aorta. A variety of histopathological assays and biochemical analyses were applied to determine gene and protein expression patterns as well as uncover underlying molecular mechanisms. CSRP2 was significantly downregulated in both human and murine AD, and CSRP2 gene overexpression dramatically reduced BAPN-induced AD incidence and prevented animal mortality. CSRP2 could preserve a contractile VSMC phenotype, even though under PDGF-BB stimulation. Mechanistically, our findings reveal that CSRP2 directly interacts with p130 Crk-associated substrate (p130Cas; also known as BCAR1) and reduces its phosphorylation, which in turn inhibits the activation of extracellular signal-regulated kinase (ERK) signaling pathways, thereby preventing VSMC phenotypic switching induced by PDGF-BB. Our findings identify CSRP2 as a novel regulator of VSMC phenotypic modulation and a significant modulator of AD development, suggesting its potential as a target for early intervention for AD.<\/jats:p>","DOI":"10.3390\/biom16081101","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:45:26Z","timestamp":1785239126000},"page":"1101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Cysteine-Rich Protein 2 in Aortic Dissection: Implications for VSMC Phenotypic Modulation\u2014CSRP2 Impedes the Progression of Aortic Dissection"],"prefix":"10.3390","volume":"16","author":[{"given":"Can","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Wanshui Road 120, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Wanshui Road 120, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"An","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Wanshui Road 120, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglin","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Wanshui Road 120, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-8313","authenticated-orcid":false,"given":"Chengxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Wanshui Road 120, Hefei 230022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2502108","DOI":"10.1002\/advs.202502108","article-title":"Ccdc80 protects against aortic dissection and rupture by maintaining the contractile smooth muscle cell phenotype","volume":"12","author":"Xiao","year":"2025","journal-title":"Adv. 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