Preservation of base-line hemodynamic function and loss of inducible cardioprotection in adult mice lacking protein kinase Cε

Signaling pathways involving protein kinase C isozymes are modulators of cardiovascular development and response to injury. Protein kinase Cepsilon activation in cardiac myocytes reduces necrosis caused by coronary artery disease. However, it is unclear whether protein kinase Cepsilon function is required for normal cardiac development or inducible protection against oxidative stress. Protein kinase Cdelta activation is also observed during cardiac preconditioning. However, its role as a promoter or inhibitor of injury is controversial. We examined hearts from protein kinase Cepsilon knock-out mice under physiological conditions and during acute ischemia reperfusion. Null-mutant and wild-type mice displayed equivalent base-line morphology and hemodynamic function. Targeted disruption of the protein kinase Cepsilon gene blocked cardioprotection caused by ischemic preconditioning and alpha(1)-adrenergic receptor stimulation. Protein kinase Cdelta activation increased in protein kinase Cepsilon knock-out myocytes without altering resistance to injury. These observations support protein kinase Cepsilon activation as an essential component of cardioprotective signaling. Our results favor protein kinase Cdelta activation as a mediator of normal growth. This study advances the understanding of cellular mechanisms responsible for preservation of myocardial integrity as potential targets for prevention and treatment of ischemic heart disease.