Abstract
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, referred to as “statins” have been extensively reported to possess lipid lowering effects by inhibiting the synthesis of cholesterol by liver and thereby increasing hepatic cholesterol uptake and reducing circulating lipid levels. Growing body of evidences have shown that apart from lipid lowering effects, statins possess various pleiotropic effects that include improvement in endothelial dysfunction, increased expression of endothelial nitric oxide synthase (eNOS), enhanced bioavailability of nitric oxide (NO), potent antioxidant potential and anti-inflammatory properties. In relation to cardiovascular pathologies, statins have been shown to inhibit atrial myocardial remodeling, prevent atrial fibrillation, conserve NO production in heart failure, reduce activity of small G-proteins in cardiac hypertrophy and protect the myocardium from lethal ischemia/reperfusion (I/R) injury. The mechanisms underlying the cardioprotective potential include phosphatidyl inositol (PI3)-kinase/Akt/eNOS pathway, subsequent activation of ATP sensitive potassium (KATP) channels by NO resulting in improved myocardial metabolism, release of endogenous adenosine by increasing the activity of adenosine forming enzyme ecto-5V-nucleotidase, inhibition of reactive oxygen species (ROS) production, decrease in oxidative stress and attenuation of apoptosis. The present review article demonstrates the pleiotropic effects of statins beyond their lipid lowering effects. Moreover, the underlying mechanisms involved in stain-induced cardioprotection have been delineated.