Statin mediated protection of the ischemic myocardium.
Hypercholesterolemia is a major risk factor in the development of cardiovascular disease and HMG-CoA reductase inhibitors (i.e. statins) were originally designed to reduce serum cholesterol levels and thus reduce this risk factor. However, it has become increasingly apparent that the effects of statins extend well beyond their lipid lowering actions, and these pleiotropic effects have a major role in protecting the myocardium against ischemic injury. There have been a large number of clinical studies demonstrating the safety and efficacy of statins in reducing total mortality as well as many other secondary endpoint markers in patients with cardiovascular disease. In addition, statins appear to benefit patients with a variety of clinical conditions such as acute coronary syndromes and severe heart failure. Recent experimental studies demonstrated that stains can rapidly (i.e. within hours) upregulate endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production. These landmark studies of statins and eNOS function set the foundation for the investigation of the protective effects of statins. Many experimental studies investigating the effects of statins on eNOS and cardiac injury in the setting of ischemia and reperfusion have been performed in an attempt to determine the extent of the protection as well as the mechanism of the protection. This review article will focus on our current understanding of statin-mediated protection of the myocardium against ischemia-reperfusion injury and infarction.
Wright
Douglas G
DG
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, United States.
Lefer
David J
DJ
D002316:Cardiotonic Agents / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*
D002316:Cardiotonic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors