Programmed death as a therapeutic target to reduce myocardial infarction.
In the United States, angioplasty or bypass surgery to remove coronary occlusions is performed on approximately two million patients each year. Although reperfusion is essential for salvaging ischemic myocardium, it also promotes infarction by activating programmed cell death in the formerly ischemic tissue. Reperfusion injury begins when oxidative stress and calcium accumulation by the mitochondria cause activation of the so-called mitochondrial death channels. These channels have become the focus of evolving strategies to protect the heart from infarction. Preclinical and preliminary clinical studies indicate that agents with diverse modes of action can reduce infarct size by 50% or more and significantly preserve myocardial functions. This article reviews the most advanced pharmacological approaches for their ability to reduce infarct size by inhibiting the mitochondrial death pathways.
Webster
Keith A
KA
Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Medical Center, 1600 NW 10(th) Avenue, RMSB 6038 Miami, FL 33101, USA. kwebster@med.miami.edu
D000818:Animals; D017209:Apoptosis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000628:therapy*; D058986:Phosphodiesterase 5 Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2