{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:50:57Z","timestamp":1774381857301,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1011394","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["22CVD03"],"award-info":[{"award-number":["22CVD03"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Smooth muscle cell-specific myosin heavy chain, encoded by <jats:italic>MYH11<\/jats:italic>, is selectively expressed in smooth muscle cells (<jats:bold>SMC<\/jats:bold>s). Pathogenic variants in <jats:italic>MYH11<\/jats:italic> predispose to a number of disorders, including heritable thoracic aortic disease associated with patent ductus arteriosus, visceral myopathy, and megacystis-microcolon-intestinal hypoperistalsis syndrome. Rare variants of uncertain significance occur throughout the gene, including <jats:italic>MYH11<\/jats:italic> p.Glu1892Asp, and we sought to determine if this variant causes thoracic aortic disease in mice. Genomic editing was used to generate <jats:italic>Myh11<\/jats:italic><jats:sup>E1892D\/E1892D<\/jats:sup> mice. Wild-type (<jats:bold>WT<\/jats:bold>) and mutant mice underwent cardiovascular phenotyping with and without transverse aortic constriction (<jats:bold>TAC<\/jats:bold>). <jats:italic>Myh11<\/jats:italic><jats:sup>E1892D\/E1892D<\/jats:sup> and WT mice displayed similar growth, blood pressure, root and ascending aortic diameters, and cardiac function up to 13 months of age, along with similar contraction and relaxation on myographic testing. The hypertension induced by TAC was similarly in <jats:italic>Myh11<\/jats:italic><jats:sup>E1892D\/E1892D<\/jats:sup> and WT mice, but mutant mice showed augmented ascending aortic enlargement and increased elastic fiber fragmentation on histology. Unexpectedly, male <jats:italic>Myh11<\/jats:italic><jats:sup>E1892D\/E1892D<\/jats:sup> mice undergoing TAC had decreased ejection fraction, stroke volume, fractional shortening, and cardiac output compared to similarly treated male WT mice. Importantly, left ventricular mass increased significantly due to primarily posterior wall thickening, and cardiac histology confirmed cardiomyocyte hypertrophy and increased collagen deposition in the myocardium and surrounding arteries. These results further highlight the phenotypic heterogeneity associated with <jats:italic>MYH11<\/jats:italic> rare variants. Given that <jats:italic>MYH11<\/jats:italic> is selectively expressed in SMCs, these results implicate a role of SMCs in the arteries of the heart contributing to cardiac hypertrophy and failure with pressure overload.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011394","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T17:33:28Z","timestamp":1752514408000},"page":"e1011394","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["MYH11 rare variant augments aortic growth and induces cardiac hypertrophy and heart failure with pressure 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