{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:08:27Z","timestamp":1790755707606,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"National Research Agency","doi-asserted-by":"publisher","award":["ANR-16-RHUS-0003"],"award-info":[{"award-number":["ANR-16-RHUS-0003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Thoracic radiotherapy can lead to cardiac remodeling including valvular stenosis due to fibrosis and calcification. The monovalent non-selective cation channel TRPM4 is known to be involved in calcium handling and to participate in fibroblast transition to myofibroblasts, a phenomenon observed during aortic valve stenosis. The goal of this study was to evaluate if TRPM4 is involved in irradiation-induced aortic valve damage. Four-month-old Trpm4+\/+ and Trpm4\u2212\/\u2212 mice received 10 Gy irradiation at the aortic valve. Cardiac parameters were evaluated by echography until 5 months post-irradiation, then hearts were collected for morphological and histological assessments. At the onset of the protocol, Trpm4+\/+ and Trpm4\u2212\/\u2212 mice exhibited similar maximal aortic valve jet velocity and mean pressure gradient. Five months after irradiation, Trpm4+\/+ mice exhibited a significant increase in those parameters, compared to the untreated animals while no variation was detected in Trpm4\u2212\/\u2212 mice. Morphological analysis revealed that irradiated Trpm4+\/+ mice exhibited a 53% significant increase in the aortic valve cusp surface while no significant variation was observed in Trpm4\u2212\/\u2212 animals. Collagen staining revealed aortic valve fibrosis in irradiated Trpm4+\/+ mice but not in irradiated Trpm4\u2212\/\u2212 animals. It indicates that TRPM4 influences irradiation-induced valvular remodeling.<\/jats:p>","DOI":"10.3390\/cancers14184477","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T22:11:10Z","timestamp":1663279870000},"page":"4477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["TRPM4 Participates in Irradiation-Induced Aortic Valve Remodeling in Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Harlyne","family":"Mpweme Bangando","sequence":"first","affiliation":[{"name":"Normandie Universit\u00e9, UR 4650, Physiopathologie et Strat\u00e9gies d\u2032Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, CHU de Caen, UNICAEN, Campus Jules Horowitz, BP 5229, 14074 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Simard","sequence":"additional","affiliation":[{"name":"Normandie Universit\u00e9, UR 4650, Physiopathologie et Strat\u00e9gies d\u2032Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, CHU de Caen, UNICAEN, Campus Jules Horowitz, BP 5229, 14074 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaux","family":"Aize","sequence":"additional","affiliation":[{"name":"Normandie Universit\u00e9, UR 4650, Physiopathologie et Strat\u00e9gies d\u2032Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, CHU de Caen, UNICAEN, Campus Jules Horowitz, BP 5229, 14074 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Lebrun","sequence":"additional","affiliation":[{"name":"Normandie Universit\u00e9, UR 4650, Physiopathologie et Strat\u00e9gies d\u2032Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, CHU de Caen, UNICAEN, Campus Jules Horowitz, BP 5229, 14074 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Manrique","sequence":"additional","affiliation":[{"name":"Normandie Universit\u00e9, UR 4650, Physiopathologie et Strat\u00e9gies d\u2032Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, CHU de Caen, UNICAEN, Campus Jules Horowitz, BP 5229, 14074 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Guinamard","sequence":"additional","affiliation":[{"name":"Normandie Universit\u00e9, UR 4650, Physiopathologie et Strat\u00e9gies d\u2032Imagerie du Remodelage Cardiovasculaire, GIP Cyceron, CHU de Caen, UNICAEN, Campus Jules Horowitz, BP 5229, 14074 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the STOP-AS Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00392-021-01809-y","article-title":"Pathomechanisms and therapeutic opportunities in radiation-induced heart disease: From bench to bedside","volume":"110","author":"Varga","year":"2021","journal-title":"Clin. 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