{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T18:47:46Z","timestamp":1782067666283,"version":"3.54.5"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["HL153710,HL166203,HL109946"],"award-info":[{"award-number":["HL153710,HL166203,HL109946"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,22]]},"abstract":"<jats:p>\n                    Abdominal aortic aneurysm (AAA) lacks effective pharmacological therapies. Here, we investigate transcription factor 7\u2013like 2 (TCF7L2), a genetic locus associated with both thoracic and abdominal aortic aneurysms, to elucidate its role in AAA pathogenesis. Integrating summary data\u2013based Mendelian randomization (SMR) with single-cell RNA sequencing of human and mouse aortae, we identify\n                    <jats:italic>TCF7L2<\/jats:italic>\n                    as a gene enriched in vascular smooth muscle cells (VSMCs) and causally linked to AAA development. Smooth muscle cell\u2013specific TCF7L2 knockout significantly attenuates AAA formation across 3 distinct murine models (AAA induced by angiotensin II infusion, by \u03b2-aminopropionitrile\/angiotensin II coadministration, and by elastase), independent of systemic blood pressure or lipid levels. Mechanistic studies reveal that TCF7L2 directly upregulates MMP14 and downregulates TIMP3 expression in vitro and in vivo, driving MMP2-mediated extracellular matrix (ECM) degradation. Concurrently, TCF7L2 represses integrin \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    (ITGB1) expression, reducing VSMC adhesion to the ECM. Collectively, these findings identify TCF7L2 as a key driver of pathological vascular remodeling in AAA, suggesting that targeting TCF7L2 may offer a novel therapeutic strategy for limiting AAA progression.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.195681","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:38:14Z","timestamp":1777567094000},"source":"Crossref","is-referenced-by-count":0,"title":["TCF7L2 promotes abdominal aortic aneurysm through smooth muscle cell\u2013mediated extracellular matrix remodeling"],"prefix":"10.1172","volume":"11","author":[{"given":"Yongjie","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."},{"name":"Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China."},{"name":"Department of Cardiology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaozhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1428-5145","authenticated-orcid":true,"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."},{"name":"Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-8986","authenticated-orcid":true,"given":"Guizhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."},{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3158-2002","authenticated-orcid":true,"given":"Zhenguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5740-8010","authenticated-orcid":true,"given":"Haocheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA."},{"name":"Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-9159","authenticated-orcid":true,"given":"Yanhong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Frankel 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