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RESEARCH PRODUCT

Should Treatment of Sepsis Include Statins?

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description

During the past decade, HMG-CoA reductase inhibitors (statins) have been shown to improve survival in patients with cardiovascular disease. Initially, the beneficial effects of statins were attributed simply to lipid reduction1; however, more recent data suggest that “pleiotropic” properties such as improvement of endothelial dysfunction, increased nitric oxide bioavailability, and antioxidative and antiinflammatory properties may contribute to the improvement of prognosis in patients with coronary artery disease. Many of these pleiotropic effects of statins are mediated by the ability to block the synthesis of important isoprenoid intermediates, which have been shown to serve as lipid attachments for a variety of intracellular signaling molecules. In particular, the inhibition of the small guanosine triphosphate–binding proteins rho, ras, and rac, the membrane localization of which depends on isoprenylation, may play an important role in mediating the direct effects of statins on the vascular wall. Thus, the characteristics of this class of drugs may explain the dramatic effects on the progression of atherosclerosis and therefore on survival in patients with established coronary artery disease.