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However, the underlying pathological mechanisms remain unclear because of a lack of animal models. In this study, we established a mouse model with <jats:italic>Myh11<\/jats:italic> K1256del, the pathogenic variant we found previously in two FTAAD families. The <jats:italic>Myh11<\/jats:italic><jats:sup>\u2206K\/\u2206K<\/jats:sup> aorta showed increased wall thickness and ultrastructural abnormalities, including weakened cell adhesion. Notably, the <jats:italic>Myh11<\/jats:italic><jats:sup>\u2206K\/+<\/jats:sup> mice developed aortic dissections and intramural haematomas when stimulated with angiotensin II. Mechanistically, integrin subunit alpha2 (<jats:italic>Itga2<\/jats:italic>) was downregulated in the <jats:italic>Myh11<\/jats:italic><jats:sup>\u2206K\/\u2206K<\/jats:sup> aortas, and the smooth muscle cell lineage cells that differentiated from <jats:italic>Myh11<\/jats:italic><jats:sup>\u2206K\/\u2206K<\/jats:sup> induced pluripotent stem cells. The contractility of the <jats:italic>Myh11<\/jats:italic><jats:sup>\u2206K\/\u2206K<\/jats:sup> aortas in response to phenylephrine was also reduced. These results imply that the suboptimal cell adhesion indicated by <jats:italic>Itga2<\/jats:italic> downregulation causes a defect in the contraction of the aorta. Consequently, the defective contraction may increase the haemodynamic stress underlying the aortic dissections.<\/jats:p>","DOI":"10.1038\/s41598-022-12418-8","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T11:03:13Z","timestamp":1653476593000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["An Myh11 single lysine deletion causes aortic dissection by reducing aortic structural integrity and contractility"],"prefix":"10.1038","volume":"12","author":[{"given":"Keita","family":"Negishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Aizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Shindo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Miyakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Tanokura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosky","family":"Kataoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyo","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Tomida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norifumi","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issei","family":"Komuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuomi","family":"Kario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"12418_CR1","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/s0741-5214(97)70261-1","volume":"25","author":"A Biddinger","year":"1997","unstructured":"Biddinger, A., Rocklin, M., Coselli, J. & Milewicz, D. 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