Abstract
Background
Calcium/calmodulin-dependent protein kinase type II delta (CamKIIδ), the predominant cardiac CaMKII isoform, has been implicated in the progression of myocardial infarction- and pressure overload-induced pathological remodeling and heart failure, but its role in volume overload (VO) has not been defined. We have previously reported an activation of CamKII during transition to HF in VO.
Purpose
Here, we analyzed the impact of CamKIIδ deletion in VO-triggered myocardial remodeling and heart failure development.
Methods
CaMKIIδ knockout (CaMKIIδ-KO) and wild-type (WT) littermates were exposed to aorto-caval shunt-induced VO, and the progression of myocardial remodeling was assessed by serial echocardiography, histological and molecular analyses.
Results
CaMKIIδ-KO and WT littermates exhibited similar mortality pattern in response to VO. Serial echocardiographic measurements showed a comparable eccentric myocardial remodeling, altered left ventricle geometry and perturbed ventricular function after shunt. At 12 weeks post-shunt both CaMKIIδ-KO and WT mice experienced comparable increases in relative heart weight, cardiomyocyte diameter, cardiac apoptosis, and hypertrophic genes expression.
Conclusion
We therefore conclude that CaMKIIδ signaling is dispensable for the progression of pathological cardiac remodeling induced by VO. This should be considered before CaMKII inhibition is approved therapeutically for HF treatment.
Activation of type II calcium/calmodulin-dependent protein kinase by Ca2+/calmodulin is inhibited by autophosphorylation of threonine within the calmodulin-binding domain.
