Statins and the response to myocardial injury.
The benefits of long-term statin (HMG-CoA reductase inhibitor) treatment for preventing coronary events have been well documented in several large-scale prospective clinical trials. By influencing the determinants of myocardial injury, statins may produce direct cardioprotective effects in the ischemic myocardium and prevent further damaging recurrent events. Although not proven fully in a clinical setting, cholesterol-independent or 'pleiotropic' effects of statins are thought to protect against myocardial injury and may occur via a number of mechanisms. Endothelial dysfunction occurs early in the development of atherosclerosis and is associated with a reduction in endothelial nitric oxide (NO) production. Statins have been shown to increase the expression of endothelial NO synthase, with subsequent augmentation of NO in the vasculature. Statins have also been reported to have anti-inflammatory effects, reducing the release of cytokines and chemokines, decreasing the expression of pro-inflammatory cell adhesion molecules, and reducing the accumulation of neutrophils in myocardial tissue following ischemia and reperfusion. Indeed, the role of statins in reducing infarct size is supported by data from a number of preclinical studies. Statin treatment, administered at the onset of reperfusion, has been shown to reduce infarct size by approximately 50% following ischemia in various animal models, and this may be an NO-dependent effect. Randomized clinical trials have indicated that early initiation of statin treatment is associated with a reduction in both the rate of recurrence of cardiovascular events and death in patients with acute coronary syndrome. In addition, decreased rates of myocardial infarction and mortality were demonstrated in several retrospective studies where statin treatment was administered before an interventional procedure. There is a need for further clinical trials to fully elucidate the importance of pre-procedural statin therapy and to determine the extent and mechanisms by which statins exert their cardioprotective effects.
Scalia
Rosario
R
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia 19107, USA. rosario.scalia@jefferson.edu
D000818:Animals; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D009569:Nitric Oxide; D000068718:Rosuvastatin Calcium