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Whether these answers to mechanical tension are mediated by specific sensors in cardiomyocytes remains elusive. In this study, the piezo2 protein was evaluated as a potential mechanosensor. Piezo2 was found to be upregulated in various rat and mouse cardiac tissues upon mechanical or pharmacological stress. To investigate its function, C57BL\/6J mice with homozygous cardiomyocyte-specific piezo2 knockout [Piezo2-KO] were created. To this end, \u03b1-MHC-Cre mice were crossed with homozygous \u201cfloxed\u201d piezo2 mice. \u03b1-MHC-Cre mice crossed with wildtype mice served as controls [WT-Cre<jats:sup>+<\/jats:sup>]. In cardiomyocytes of Piezo2-KO mice, piezo2 mRNA was reduced by\u2009&gt;\u200990% and piezo2 protein was not detectable. Piezo2-KO mice displayed no morphological abnormalities or altered cardiac function under nonstressed conditions. In a subsequent step, hearts of Piezo2-KO or WT-Cre<jats:sup>+<\/jats:sup>-mice were stressed by either three weeks of increased afterload (angiotensin II, 2.5\u00a0mg\/kg\/day) or one week of hypercontractility (isoprenaline, 30\u00a0mg\/kg\/day). As expected, angiotensin II treatment in WT-Cre<jats:sup>+<\/jats:sup>-mice resulted in higher heart and lung weight (per body weight,\u2009+\u200938%,\u2009+\u200942%), lower ejection fraction and cardiac output (\u2212\u00a030%, \u2212\u00a039%) and higher left ventricular anterior and posterior wall thickness (+\u200934%,\u2009+\u200937%), while isoprenaline led to higher heart weight (per body weight,\u2009+\u200925%) and higher heart rate and cardiac output (+\u200924%,\u2009+\u200954%). The Piezo2-KO mice reacted similarly with the exception that the angiotensin II-induced increases in wall thickness were blunted and the isoprenaline-induced increase in cardiac output was slightly less pronounced. As cardiac function was neither severely affected under basal nor under stressed conditions in Piezo2-KO mice, we conclude that piezo2 is not an indispensable mechanosensor in cardiomyocytes.<\/jats:p>","DOI":"10.1038\/s41598-022-12085-9","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T13:04:11Z","timestamp":1652792651000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Piezo2 is not an indispensable mechanosensor in murine cardiomyocytes"],"prefix":"10.1038","volume":"12","author":[{"given":"Benjamin","family":"Kloth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Mearini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Weinberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Stenzig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Geertz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Starbatty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Lindner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Reichenspurner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Eschenhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc N.","family":"Hirt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"12085_CR1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/j.yjmcc.2009.12.017","volume":"48","author":"PP de Tombe","year":"2010","unstructured":"de Tombe, P. 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