Mechanisms of cell survival in myocardial hibernation.
Myocardial hibernation represents a condition of regional ventricular dysfunction in patients with chronic coronary artery disease, which reverses gradually after revascularization. The precise mechanism mediating the regional dysfunction is still debated. One hypothesis suggests that chronic hypoperfusion results in a self-protecting downregulation in myocardial function and metabolism to match the decreased oxygen supply. An alternative hypothesis suggests that the myocardium is subject to repetitive episodes of ischemic dysfunction resulting from an imbalance between myocardial metabolic demand and supply that eventually creates a sustained depression of contractility. It is generally agreed that hibernating myocardium is submitted repeatedly to ischemic stress, and therefore one question persists: how do myocytes survive in the setting of chronic ischemia? The hallmark of hibernating myocardium is a maintained viability of the dysfunctional myocardium which relies on an increased uptake of glucose. We propose that, in addition to this metabolic adjustment, there must be molecular switches that confer resistance to ischemia in hibernating myocardium. Such mechanisms include the activation of a genomic program of cell survival as well as autophagy. These protective mechanisms are induced by ischemia and remain activated chronically as long as either sustained or intermittent ischemia persists.
Depre
Christophe
C
Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry New Jersey, New Jersey Medical School, Newark, 07103, USA.
Vatner
Stephen F
SF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D003326:Coronary Circulation; D006321:Heart / Q000503:physiopathology*; D006706:Homeostasis; D006801:Humans; D017202:Myocardial Ischemia / Q000235:genetics; D017682:Myocardial Stunning / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism
D002118:Calcium