Statins and autoimmune diseases

Inhibitors of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase or statins are effective lipid lowering drugs. The lipid lowering activity is mainly achieved through reduction of cholesterol synthesis and up-regulation of low density lipoprotein receptors that in turn clear low density lipoproteins and low density lipoprotein precursors from the blood. HMG-CoA reductase competitively blocks mevalonate, the enzyme reaction product that is the precursor not only of cholesterol but also of several non-steroidal isoprenoid compounds. Isoprenoids allow the attachment to the cell membrane of signalling proteins involved in various cell functions; their inhibition explains the so-called pleiotropic effects of statins, which include anti-inflammatory anticoagulant and immunomodulatory properties. Such pleiotropic activities have been suggested to justify the benefits of statin therapy besides the simple reduction in plasma cholesterol levels. Accelerated atherosclerosis has been reported in several autoimmune rheumatic diseases. Non-traditional risk factors for atherosclerosis, such as inflammation, immune-mediated responses and thrombophilia, have been suggested to play a major role in sustaining premature atherosclerosis in autoimmune rheumatic diseases. This review focuses on the potential use of statins as a new therapeutical tool for treating autoimmune rheumatic diseases based on their antiatherosclerotic activity and on their pleiotropic effect on inflammation, haemostasis and the immune responses.