Figure 1.

Pleiotropic effects of statins. The lipid lowering effects of statins is attributed to their action on 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA reductase). Statins block the pathway for synthesizing cholesterol in liver by competitively inhibiting HMG-CoA reductase, the rate-controlling enzyme of the mevalonate pathway, leading to lower circulating low-density lipoprotein (LDL) cholesterol levels. A decrease in cholesteryl ester transfer protein (CETP) results in a modest increase in apolipoprotein A-I and high-density lipoprotein (HDL) cholesterol levels. Through the upregulation of endothelial nitric oxide synthase (eNOS), statins promote nitric oxide production and enhance endothelium-dependent vasodilatation. Statins also modulate the endothelial expression of cytokines, chemokines and leukocyte adhesion molecules, decreasing vascular inflammation—an important contributor to the vascular atherogenetic process. Furthermore, affecting both the endothelial production of inflammatory factors and cholesterol uptake, statins stabilize the atheromatic plaques. Their benefit on vascular function is also associated with the downregulation of nicotinamide adenine dinucleotide phosphate (NADPH) which results in lower levels of reactive oxygen species (ROS). Their antioxidative effects are also reflected on a decrease in oxidized LDL (oxLDL) levels. Statins elicit downregulation of tissue factor (TF) and overexpression of thrombomodulin, showing antithrombotic properties. Finally, the potential systematic beneficial effect of statins on systemic inflammatory diseases can be attributed to their ability to reduce inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukins, and C-reactive protein (CRP).