Anti-inflammatory and immunomodulatory effects of statins

Anti-inflammatory and immunomodulatory effects of statins. 3-Hydroxy-3-methyl-gutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins constitute the most powerful class of lipid-lowering drugs. Clinical trials have demonstrated a marked reduction in cardiovascular mortality in patients treated with statins. However, the benefits observed with statin therapy appear to be related, at least in part, with their cholesterol-lowering independent effects. Extensive research carried out mainly in the last decade suggests that the clinical benefits of these drugs could be related to an improvement in endothelial dysfunction, a reduction in blood thrombogenicity, anti-inflammatory properties, and, recently, immunomodulatory actions. In this sense, statins decrease T cell activation, the recruitment of monocytes and T cells into the arterial wall, and enhance the stability of atherosclerotic lesions. Many of these effects are related with the inhibition of isoprenoid synthesis, which serve as a lipid attachment for a variety of proteins implicated in intracellular signaling. In fact, small G proteins, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in the lipid-lowering independent effects of HMG-CoA reductase inhibitors. This article summarizes the anti-inflammatory and immunomodulatory effects of statins and their participation in the different steps of atherosclerotic lesion formation.