| First Author | Mohamed BA | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 9889 |
| PubMed ID | 31285482 | Mgi Jnum | J:285650 |
| Mgi Id | MGI:6387370 | Doi | 10.1038/s41598-019-46332-3 |
| Citation | Mohamed BA, et al. (2019) Genetic deletion of calcium/calmodulin-dependent protein kinase type II delta does not mitigate adverse myocardial remodeling in volume-overloaded hearts. Sci Rep 9(1):9889 |
| abstractText | Calcium/calmodulin-dependent protein kinase type II delta (CaMKIIdelta), the predominant CaMKII isoform expressed in the heart, has been implicated in the progression of myocardial infarction- and pressure overload-induced pathological remodeling. However, the role of CaMKIIdelta 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 CaMKIIdelta is critically involved in the mortality, myocardial remodeling, and heart failure (HF) progression in response to VO. CaMKIIdelta knockout (delta-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 delta-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 delta-KO versus WT hearts after shunt. Therefore, CaMKIIdelta signaling seems to be dispensable for the progression of VO-induced maladaptive cardiac remodeling. Accordingly, we hypothesize that CaMKIIdelta-inhibition as a therapeutic approach might not be helpful in the context of VO-triggered HF. |
