Epsilon protein kinase C as a potential therapeutic target for the ischemic heart

Ischemic heart disease is the leading cause of morbidity and mortality in the western world. Ischemic damage can occur by acute myocardial infarction, stable angina, cardiac stunning, and myocardial hibernation. In addition, 'scheduled' ischemic events, occurring during cardiac surgery, heart transplantation, and elective angioplasty, can also result in cardiac damage. Ischemic or pharmacological preconditioning can decrease the extent of damage to the myocardium. Although the mechanism of preconditioning-mediated cardioprotection is not fully understood, epsilon PKC has been implicated as a critical mediator of this process in animal studies. The use of isozyme-specific pharmacological tools has permitted a better elucidation of the upstream stimuli and the downstream transducers of epsilon PKC in the pathways leading to cardioprotection. While little is known about the role of epsilon PKC in these pathways in humans, animal studies suggest a potential therapeutic role of epsilon PKC. This review will focus on the role of epsilon PKC in cardiac protection and on the signal transduction cascades that have been implicated in this protection. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.