Role of Statins in the Inflammatory Response
Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is the rate-limiting step in cholesterol biosynthesis. These drugs are widely prescribed for the treatment of hypercholesterolemia. In addition to their plasma cholesterol lowering ability, statins have been found to have pleiotropic effects including improved endothelial function, thrombosis control, enhanced stability of atherosclerotic plaques, and decreased oxidative stress. These pleiotropic effects, while contributing to beneficial effects on cardiovascular disease, also seem to play a role in other immune and inflammatory diseases. In particular, statins have been shown to reduce risks related to sepsis in human clinical studies and to improve survival in murine models of sepsis. We are investigating how statins modulate the response of macrophages to lipopolysaccharide, a component of the outer membrane of gram-negative bacteria, which plays a role in sepsis.