{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:49:29Z","timestamp":1785451769929,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Education, Culture, Sports, Science and Technology of Japan","award":["18K08046"],"award-info":[{"award-number":["18K08046"]}]},{"name":"the Ministry of Education, Culture, Sports, Science and Technology of Japan","award":["18H02811"],"award-info":[{"award-number":["18H02811"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several genetic defects, including a mutation in myosin heavy chain 11 (Myh11), are reported to cause familial thoracic aortic aneurysm and dissection (FTAAD). We recently showed that mice lacking K1256 of Myh11 developed aortic dissection when stimulated with angiotensin II, despite the absence of major pathological phenotypic abnormalities prior to stimulation. In this study, we used a comprehensive, data-driven, unbiased, multi-omics approach to find underlying changes in transcription and metabolism that predispose the aorta to dissection in mice harboring the Myh11 K1256del mutation. Pathway analysis of transcriptomes showed that genes involved in membrane transport were downregulated in homozygous mutant (Myh11\u0394K\/\u0394K) aortas. Furthermore, expanding the analysis with metabolomics showed that two mechanisms that raise the cytosolic Ca2+ concentration\u2014multiple calcium channel expression and ADP\u2013ribose synthesis\u2014were attenuated in Myh11\u0394K\/\u0394K aortas. We suggest that the impairment of the Ca2+ influx attenuates aortic contraction and that suboptimal contraction predisposes the aorta to dissection.<\/jats:p>","DOI":"10.3390\/ijms242015213","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T01:31:22Z","timestamp":1697419882000},"page":"15213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multi-Omics of Familial Thoracic Aortic Aneurysm and Dissection: Calcium Transport Impairment Predisposes Aortas to Dissection"],"prefix":"10.3390","volume":"24","author":[{"given":"Shota","family":"Tomida","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamaki","family":"Ishima","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daigo","family":"Sawaki","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Imai","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[{"name":"Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Aizawa","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan"},{"name":"Clinical Pharmacology Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Tochigi, Japan"},{"name":"Division of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cjca.2015.11.007","article-title":"The Expanding Clinical Spectrum of Extracardiovascular and Cardiovascular Manifestations of Heritable Thoracic Aortic Aneurysm and Dissection","volume":"32","author":"Bradley","year":"2016","journal-title":"Can. 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