Endothelial Lipase as a Potential Pharmacologic Target

Epidemiologic studies have indicated a very strong inverse association between HDL-cholesterol levels and the incidence of arteriosclerotic cardiovascular disease [32]. HDL is thought to promote efflux of cholesterol from peripheral cells in the vascular wall and return of that cholesterol to the liver for excretion in bile, a process known as reverse cholesterol transport [21]. HDL has also been shown to have anti-inflammatory and anti-thrombotic activities [21]. Therefore, HDL levels may influence both the hyperlipidemia and inflammatory processes proposed as factors in the development of atherosclerosis. Although clinical data in support of HDL-raising are limited, in the VA-HIT trial gemfibrozil therapy in men with coronary artery disease and low HDL-cholesterol modestly increased HDL levels and reduced coronary events by 22% [33]. Presently, other methods of effectively and safely increasing HDL-cholesterol levels have not been discovered. 

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2 SANTAMARINA-FofO, S., HauDENSCHILD, C., and Amar, M. The role of hepatic lipase in lipoprotein metabolism and 

Perrone, M., and Rader, D.J. A novel endothelial-derived lipase that modulates HDL metabolism. Nat. Genet., 1999, 23, 424-428. 

4 Hirata, K., Diechek, H.L., Cioeei, J.A., Choi, S.Y., Leeper, N.J., Quintana, L., Kronmal, G.S., Cooper, A. D., and Quertermous, I. Cloning of a unique lipase from endothelial cells extends the lipase gene family. J. Biol. Chem., 1999, 274, 14170-14175. 

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