Ref: Goodman and Gillman, Pharmacological Basis of Therapeutics, 11th edition and Liao, J. and Laufs, U. Pleiotropic Effects of Statins. Annu. Rev. Pharmacol., 2005, 45:89-118Explanation:"Although the statins clearly exert their major effects on CHI) by lowering LDL-C and improving the lipid profile as reflected in plasma cholesterol levels, a multitude of potentially cardioprotective effects are being ascribed to these drugs. However, the mechanisms of action for non-lipid-lowering roles of statins have not been established, and it is not known whether these potential pleiotropic effects represent a class-action effect, differ among statins, or are biologically or clinically relevant....Statin therapy enhances endothelial production of the vasodilator nitric oxide, leading to improved endothelial function .... Statins may affect plaque stability in a variety of ways. They reportedly inhibit monocyte infiltration into the artery wall in a rabbit model and inhibit macrophage secretion of matrix metalloproteinases in vitro. The metalloproteinases degrade extracellular matrix components and thus weaken the fibrous cap of atherosclerotic plaques.........Statins modulate the ceUularity of the artery wall by inhibiting proliferation of smooth muscle cells and enhancing apoptotic cell death. Reduced proliferation of smooth muscle cells and enhanced apoptosis could retard initial hyperplasia and restenosis.........Statins decreased the risk of CUD and levels of C-reactive protein f an independent marker for inflammation and high CHD risk) independently of cholesterol lowering..........Statins reduce the susceptibility of lipoproteins to oxidation both in vitro and ex vivo........Statins reduce platelet aggregation and reduce the deposition of platelet thrombi in the porcine aorta model......."Ref: Goodman and GillmanPLEIOTROPIC EFFECTS OF STATINSPleiotropic effects - are 'non lipid lowering- effects of statins which offer cardioprotection.Cholesterol-independent or "pleiotropic" effects of statins involve improving:o Endothelial function.o Enhancing the stability of atherosclerotic plaques.o Decreasing oxidative stress, o Decreasing inflammation, o Inhibiting the thrombogenic response.Many of these pleiotropic effects are mediated by inhibition of isoprenoids. which serve as lipid attachments for intracellular signaling molecules.Inhibition of small GTP-binding proteins. Rho. Ras and Rac, whose proper membrane localization and function are dependent on isoprenylation. may play an important role in mediating the pleiotropic effects of statins.Statins also have beneficial extrahepatic effects on the immune system. CNS and bone.Note:Reduced LDL cholesterol is due to lipid lowering effect of statins and not pleiotropic effect.Cholesterol-independent or "pleiotropic" effects of statinsImproving endothelial function.Enhancing the stability of atherosclerotic plaques.Decreasing oxidative stress and inflammation.Inhibiting the thrombogenic response.Attenuating vascular and myocardial remodeling.Inhibiting vascular inflammation.Inhibiting oxidation.