HMG-CoA reductase inhibitors were developed for the treatment of lipid disorders and have been proved to reduce cardiovascular morbidity and mortality when used for primary or secondary prevention. The most important positive pleiotropic effects of statins are anti inflammatory, antiproliferative, and antithrombotic ones, improving endothelial dysfunction and immunomodulatory. However, by inhibiting HMG-CoA reductase, statins can also inhibit the synthesis of isoprenoids, which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42. Therefore, it is possible that statins might exert cholesterol-independent or ‘pleiotropic’ effects through direct inhibition of these small GTP binding proteins statins have several anti-inflammatory and immunomodulatory effects through which they may modify the inflammatory mechanisms involved in the generation and rupture of atherosclerotic plaques. These effects may also be useful for controlling rheumatoid inflammation. Thus statins may be an important adjunctive therapy in RA, aiming to both reduce joint inflammation and improve cardiovascular outcome.
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