Statins as potent antiinflammatory drugs.

Abstract

Statin drugs have previously been shown to very significantly reduce cardiovascular disease events in a number of large clinical trials.1 As a result, statins are now considered to represent one of the most powerful classes of agents for the treatment of cardiovascular diseases.2 Statins are rapidly becoming frontline therapy for diabetes mellitus, hypertension, and other known cardiovascular disease risk factors. Originally, reductions in cardiovascular disease events and mortality and overall improved outcomes were attributed to dramatic reductions in circulating serum lipid levels that were mediated by inhibition of liver 3-hydroxy 3-methyl glutaryl coenzyme A (HMG-CoA) reductase.1 However, more recent experimental and clinical investigations have revealed that statins can exert a number of cholesterol-independent, cardioprotective actions. In this regard, statins are potent modulators of endothelial cell nitric oxide synthase (eNOS) function and have been shown to upregulate eNOS enzyme levels and nitric oxide (NO) synthesis.3–5⇓⇓ See p 2104 Pruefer and colleagues6 now demonstrate in this issue of Circulation powerful antiinflammatory properties of simvastatin in the setting of Staphylococcus aureus α-toxin infection. Endotoxemia represents a potent stimulus for vascular inflammation that is characterized by enhanced leukocyte recruitment to the microvascular endothelium. The report by Pruefer et al6 elegantly demonstrates that pretreatment with clinically relevant doses of simvastatin attenuates endotoxin-induced leukocyte rolling and transmigration …