Pleiotropic effects of statin therapy: molecular mechanisms and clinical results.
Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for cholesterol biosynthesis, and are beneficial in the primary and secondary prevention of cardiovascular disease. Most of the benefits of statin therapy are owing to the lowering of serum cholesterol levels. 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. Recent studies have shown that statins might have important roles in diseases that are not mediated by cholesterol. Here, we review data from recent clinical trials that support the concept of statin pleiotropy and provide a rationale for their clinical importance.
Wang
Chao-Yung
CY
Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, Cambridge, MA 02139, USA.
Liu
Ping-Yen
PY
Liao
James K
JK
D002784:Cholesterol / Q000097:blood; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007155:Immunologic Factors; D013729:Terpenes / Q000037:antagonists & inhibitors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors; D013729:Terpenes; D002784:Cholesterol; D019204:GTP-Binding Proteins