{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T18:04:31Z","timestamp":1775325871238,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research on Grants-in-Aid for Research Activity Start-up","award":["22K20922"],"award-info":[{"award-number":["22K20922"]}]},{"name":"the Mochida Memorial Foundation for Medical and Pharmaceutical Research","award":["22K20922"],"award-info":[{"award-number":["22K20922"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pathogenic variants of MYH11, which encode smooth muscle myosin heavy chain 11, have been linked to familial thoracic aortic aneurysms and dissections (FTAAD). However, molecular pathways affected by these mutations have not been well understood. To explore downstream consequences of Myh11 disruption, we analyzed transcriptomic and proteomic profiles of aortas from male Myh11 mice with homozygous deletion of lysine 1256 (K1256) and of wild-type controls. Of 6499 proteins quantified, 1763 were differentially expressed (adjusted p &lt; 0.05), including 942 that were downregulated and 821 that were upregulated in mutant aortas. Enrichment analysis of downregulated genes and proteins revealed a consistent reduction in extracellular matrix-related pathways. Among downregulated proteins, we identified tenascin Xb, transforming growth factor \u03b2 (Tgfb) 2, and Tgfb receptor 1\/2, malfunctions of which are linked to connective tissue diseases, such as Ehlers\u2013Danlos and Loeys\u2013Dietz syndromes. Nevertheless, unlike these syndromic diseases, mice with Myh11 pathogenic variants and patients with FTAAD do not exhibit syndromic features, likely reflecting expression of Myh11 restricted to smooth muscle. These results suggest that loss of Myh11 disrupts maintenance of extracellular matrix by SMCs, the loss of which contributes to aortic fragility without affecting other tissues.<\/jats:p>","DOI":"10.3390\/ijms26167853","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T15:44:21Z","timestamp":1755186261000},"page":"7853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of Myh11 K1256 Dysregulates the Extracellular Matrix and Focal Adhesion by Inhibiting Zyxin-Activated Transcription"],"prefix":"10.3390","volume":"26","author":[{"given":"Shota","family":"Tomida","sequence":"first","affiliation":[{"name":"Department of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Tochigi 329-0498, Japan"},{"name":"School of Medicine, Faculty of Medicine, Gunma University, Gunma 371-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Okuhata","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Tochigi 329-0498, Japan"},{"name":"School of Medicine, Faculty of Medicine, Gunma University, Gunma 371-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2309-265X","authenticated-orcid":false,"given":"Tamaki","family":"Ishima","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Tochigi 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[{"name":"Jichi Medical University, Tochigi 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Aizawa","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Tochigi 329-0498, Japan"},{"name":"Clinical Pharmacology Center, Jichi Medical University Hospital, Tochigi 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1001\/jama.283.7.897","article-title":"The International Registry of Acute Aortic Dissection (IRAD)New Insights Into an Old Disease","volume":"283","author":"Hagan","year":"2000","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8844","DOI":"10.1038\/s41598-022-12418-8","article-title":"An Myh11 single lysine deletion causes aortic dissection by reducing aortic structural integrity and contractility","volume":"12","author":"Negishi","year":"2022","journal-title":"Sci. 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