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, epsilonPKC 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 epsilonPKC in the pathways leading to cardioprotection. While little is known about the role of epsilonPKC in these pathways in humans, animal studies suggest a potential therapeutic role of epsilonPKC. This review will focus on the role of epsilonPKC in cardiac protection and on the signal transduction cascades that have been implicated in this protection.
Inagaki
Koichi
K
Department of Molecular Pharmacology, Stanford University School of Medicine, CCSR, Room 3145A, 269 Campus Drive Stanford, CA 94305-5174, United States.
Churchill
Eric
E
Mochly-Rosen
Daria
D
D000818:Animals; D020536:Enzyme Activators / Q000627:therapeutic use; D016027:Heart Transplantation; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D020536:Enzyme Activators; D017382:Reactive Oxygen Species; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D051744:Protein Kinase C-epsilon