Non-lipid-lowering effects of statins on atherosclerosis.

Lipid and nonlipid mechanisms contribute to the beneficial effects of some statins on endothelial function, plaque stability and thrombus formation. The nonlipid effects of statins may contribute to alleviation of tissue ischemia and prevention of acute cardiovascular syndromes. Endothelial dysfunction is reversed by a statin and this beneficial property results, in part, from direct actions on the endothelial vasoactive factors, nitric oxide and endothelin-1. Some statins have been shown to inhibit production of proinflammatory cytokines that regulate many key functions of the vascular wall including monocyte adhesion, chemotaxis, and metalloproteinase secretion. Vascular smooth muscle cell synthetic capacity and viability is inhibited by lipophilic agents, whereas a hydrophilic agent does not interfere with this reparative response. Some statins may impede thrombogenesis by reduced activation of the extrinsic coagulation pathway, inhibition of platelet adhesion and aggregation, and improvement in the rheologic profile.