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TAAD etiology and pathogenesis suggest that alteration of mechanical force propagation may contribute to SMC dysfunction. This study aims to determine the role of SMC focal adhesion proteins, which are key components of force transmission, in TAAD pathogenesis. scRNA-seq analysis of human TAA aortas showed reduced expression of intracellular focal adhesion components, including\n                    <jats:italic>PTK2<\/jats:italic>\n                    (FAK),\n                    <jats:italic>VCL<\/jats:italic>\n                    ,\n                    <jats:italic>ILK<\/jats:italic>\n                    , and\n                    <jats:italic>TES<\/jats:italic>\n                    transcripts, in SMCs. Additionally, protein levels of FAK, ILK, and VCL were decreased in the aorta of patients with TAA. SMC-specific\n                    <jats:italic>Ptk2<\/jats:italic>\n                    ,\n                    <jats:italic>Vcl<\/jats:italic>\n                    , and\n                    <jats:italic>Ilk<\/jats:italic>\n                    KO mice treated with \u03b2-aminopropionitrile (BAPN) exhibited increased mortality, aortic dilation, ECM breakdown, and SMC loss. Mechanistically, knocking down FAK, ILK, and VCL exacerbated gliotoxin-induced SMC anoikis, whereas overexpressing full-length WT and dead-kinase FAK conferred resistance to apoptosis and cell detachment, indicating that FAK\u2019s protective effects depend on its expression rather than its enzymatic activity. Inhibition of FAK kinase activity did not affect SMC apoptosis in vitro or aortic dilation in vivo. Our findings demonstrate that the expression of focal adhesion proteins protects against TAAD progression and SMC anoikis independently of FAK kinase activity.\n                  <\/jats:p>\n                  <jats:p\/>\n                  <jats:p>Focal adhesion proteins help prevent aortic wall weakening by supporting smooth muscle cell survival and resisting anoikis, offering new insight into aneurysm progression and potential treatments.<\/jats:p>","DOI":"10.1172\/jci.insight.195291","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:00:17Z","timestamp":1774368017000},"source":"Crossref","is-referenced-by-count":0,"title":["Focal adhesion proteins confer smooth muscle anoikis resistance and protection against aortic aneurysm and dissection"],"prefix":"10.1172","volume":"11","author":[{"given":"Zhenyuan","family":"Zhu","sequence":"first","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"School of Medicine, Tsinghua University, Beijing, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxin","family":"Wei","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepa","family":"Suryanarayan","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parya","family":"Behzadi","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Edgar","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie A.","family":"Phillippi","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery,"},{"name":"Department of Bioengineering, Swanson School of Engineering, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"St. Hilaire","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Cardiothoracic Surgery,"},{"name":"Department of Bioengineering, Swanson School of Engineering, and"},{"name":"Department of Medicine, Division of Cardiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Espinosa-Diez","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Center for Molecular Medicine and Genetics, Department of Physiology, Wayne State School of Medicine, Detroit, Michigan, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delphine","family":"Gomez","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Medicine, Division of Cardiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2016.01.017"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312436"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy006"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.009762"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312131"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2009.07.075"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314670"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046528"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0"},{"issue":"4","key":"B10","first-page":"336","article-title":"Altered secretion of type III procollagen in a form of type IV Ehlers-Danlos syndrome. 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