Statins and the vascular endothelial inflammatory response

Statins reduce cholesterol synthesis and are widely used for the treatment of hyperlipidaemia and ischaemic heart disease. Besides their cholesterol-lowering effects, statins also possess broad immunomodulatory and antiinflammatory properties. Vascular endothelial cells have a crucial role in the pathogenesis of inflammatory disease, and, alongside leukocytes and antigen-presenting cells, represent a key cellular target for statin therapy. Recent studies investigating how these drugs modify endothelial cell function demonstrate that the therapeutic effect of statins can be attributed, in part, to their action on the endothelium. Accordingly, statins attenuate endothelial MHC class II expression, increase endothelial nitric oxide synthase and fibrinolytic activity, decrease leukocyte adhesion and transmigration, and enhance resistance to local injurious stimuli. Many of these effects are brought about by the modulation of small GTPase function and the downregulation of promflammatory gene expression.