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Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We sought to determine if hypertension in combination with a \u201cvariant of uncertain significance\u201d that disrupts protein function, <jats:italic>MYH11<\/jats:italic> p.Arg247Cys, would induce aortic dissections in a mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Approach and results<\/jats:title><jats:p>Administration of L-NAME via drinking water and a high salt diet increased blood pressure in WT and <jats:italic>Myh11<jats:sup>R247C\/R247C<\/jats:sup><\/jats:italic> mice and triggered type A dissections with cardiac tamponade in 20% of the <jats:italic>Myh11<jats:sup>R247C\/R247C<\/jats:sup><\/jats:italic> mice. <jats:italic>Myh11<jats:sup>R247C\/R247C<\/jats:sup><\/jats:italic> aortas have aberrant smooth muscle contractile unit-elastin connections by transmission electron microscopy, along with increased focal adhesion signaling at baseline, which further increases with hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Gene-environment interactions trigger aortic dissections in <jats:italic>Myh11<jats:sup>R247C\/R247C<\/jats:sup><\/jats:italic> mice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2025.1492768","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T06:57:48Z","timestamp":1739516268000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Inducing hypertension in Myh11R247C\/R247C mice triggers aortic dissections with increased focal adhesion kinase signaling"],"prefix":"10.3389","volume":"12","author":[{"given":"Callie S.","family":"Kwartler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanzhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pujun","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Yan","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine C.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.ahj.2011.06.020","article-title":"Susceptibility to acute thoracic aortic dissections in patients dying outside the hospital: an autopsy study","volume":"162","author":"Prakash","year":"2011","journal-title":"Am Heart J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/ccd.22537","article-title":"2010 ACCF\/AHA\/AATS\/ACR\/ASA\/SCA\/SCAI\/SIR\/STS\/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: executive summary. 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