{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T19:24:43Z","timestamp":1787858683851,"version":"build-2784847793"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Thoracic aortic aneurysms and dissections (TAAD) are life\u2010threatening vascular disorders affecting the medial layer of the aortic wall, associated with high mortality when a rupture or dissection occurs. Though numerous genes are associated with familial TAAD (FTAAD), pathogenic variants in\n                      <jats:italic>MYH11<\/jats:italic>\n                      , encoding smooth muscle cell specific myosin heavy chain (SM\u2010MHC), represent a rare but interesting subgroup as many gaps remain in the knowledge of disease mechanisms, phenotype presentation and gene\u2013environmental interactions. No reliable therapy exists in halting aneurysm growth in affected individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Scope of Review<\/jats:title>\n                    <jats:p>This review aims to summarize current evidence on disease pathophysiological mechanisms. Furthermore, phenotypic variability, extrathoracic vascular involvement and the possibility of future curative gene therapy options are evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Most reported pathogenic\n                      <jats:italic>MYH11<\/jats:italic>\n                      variants are missense or splice\u2010site variants that disrupt the C\u2010terminal coiled\u2010coil dimerization and therefore thick filament assembly. Evidence from mouse models, patient\u2010derived cells and limited human ex\u00a0vivo tissue studies shows that these variants are associated with impaired thick filament organization, reduced force generation and disruption of the elastin\u2010contractile unit, with subsequent alterations in ECM remodelling. However, the precise causal sequence in human disease has not yet been established. Clinically,\n                      <jats:italic>MYH11\u2010<\/jats:italic>\n                      associated disease is associated with FTAAD and patent ductus arteriosus (PDA). Reduced penetrance, variable expression of disease and unknown potential gene\u2013environment interactions complicate risk prediction and clinical counselling of affected individuals. Emerging RNA\u2010therapy strategies aimed at allele\u2010specific correction of genetic disease offer interesting future therapeutic targets, although vascular delivery and long\u2010term safety remain challenges.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MYH11<\/jats:italic>\n                      should be viewed as a clinically meaningful gene that is associated with TAAD and PDA. Current limited evidence shows that the phenotype is characterized by contractile dysfunction, increased aortic stiffness and potential susceptibility to hemodynamic stress. Future work should investigate translatable mechanistic studies, larger registries for genotype\u2013phenotype correlations and evaluation of targeted gene therapy approaches.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70196","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T10:01:28Z","timestamp":1774605688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MYH11 variants in thoracic aortic aneurysm pathophysiology: From bench to bedside"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5406-5953","authenticated-orcid":false,"given":"Aria","family":"Atash","sequence":"first","affiliation":[{"name":"Department of Cardiology, Division Heart and Lungs University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barend M. 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