Statins, inhibitors of 3-hydroxy-3-methylglutaryl
coenzyme A reductase, have been used successfully in the treatment of
hypercholesterolemia for more than a decade.
Statins also exhibit overall clinical benefits on
cardiovascular diseases independent of their effects on lowering serum
cholesterol levels. These beneficial effects of
statin therapy are believed to be due, at least in part, to the anti-inflammatory and immunomodulatory roles of
statins.
Statin treatment reduces the levels of inflammatory markers, decreases the activation and recruitment of immune cells, and delays the progression of
atherosclerosis, a chronic inflammatory disease. However, little is known about the direct impact of
statins on immune cells, particularly on macrophages. We report that
lovastatin, a member of the
statin family, effectively induces apoptosis in macrophages. Further investigation of the molecular mechanism has revealed that Rac1 and Cdc42, the
small GTPase family members, may play an important role in
lovastatin-induced macrophage apoptosis. Moreover, the activation of the JNK pathway may contribute to this event. Our findings provide a better understanding of the molecular basis underlying the anti-inflammatory clinical benefits of
statin therapy in
cardiovascular diseases.