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However, the role of CaMKII\u03b4 in volume overload (VO) has not been explored. We have previously reported an activation of CaMKII during transition to HF in long-term VO. Here, we address whether CaMKII\u03b4 is critically involved in the mortality, myocardial remodeling, and heart failure (HF) progression in response to VO. CaMKII\u03b4 knockout (\u03b4-KO) and wild-type (WT) littermates were exposed to aortocaval shunt-induced VO, and the progression of adverse myocardial remodeling was assessed by serial echocardiography, histological and molecular analyses. The mortality rates during 10 weeks of VO were similar in \u03b4-KO and WT mice. Both genotypes displayed comparable eccentric myocardial hypertrophy, altered left ventricle geometry, perturbed systolic and diastolic functions after shunt. Additionally, cardiomyocytes hypertrophy, augmented myocyte apoptosis, and up-regulation of hypertrophic genes were also not significantly different in \u03b4-KO versus WT hearts after shunt. Therefore, CaMKII\u03b4 signaling seems to be dispensable for the progression of VO-induced maladaptive cardiac remodeling. Accordingly, we hypothesize that CaMKII\u03b4-inhibition as a therapeutic approach might not be helpful in the context of VO-triggered HF.<\/jats:p>","DOI":"10.1038\/s41598-019-46332-3","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T10:31:59Z","timestamp":1562581919000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic deletion of calcium\/calmodulin-dependent protein kinase type II delta does not mitigate adverse myocardial remodeling in volume-overloaded hearts"],"prefix":"10.1038","volume":"9","author":[{"given":"Belal A.","family":"Mohamed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manar","family":"Elkenani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Jakubiczka-Smorag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3452-8017","authenticated-orcid":false,"given":"Eric","family":"Buchholz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Koszewa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawid","family":"Lbik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz","family":"Schnelle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Hasenfuss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Toischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,7,8]]},"reference":[{"key":"46332_CR1","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/S0140-6736(06)68074-4","volume":"367","author":"LH Opie","year":"2006","unstructured":"Opie, L. 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