The role of endothelial lipase in high-density lipoprotein metabolism

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Abstract
Elevating high-density lipoprotein levels is increasingly being identified as an essential strategy for the prevention of atherosclerosis. Plasma levels of high-density lipoprotein cholesterol and its major protein, apoAI, are largely influenced by the rate of turnover. Lipases play an important role in modulating the metabolism of high-density lipoprotein. In particular, endothelial lipase has been shown to be an important determinant of high-density lipoprotein metabolism and levels in murine models. This article reviews new developments in our understanding of the biology of endothelial lipase and its relation to high-density lipoprotein metabolism. Inhibition of the endothelial lipase gene, either by antibody injection or by targeted gene deletion, results in an approximately 50% increase in high-density lipoprotein cholesterol levels in mice. As many as 31 single-nucleotide polymorphisms have been identified in the endothelial lipase gene. The 584 C/T mutation, which results in a threonine-to-isoleucine amino acid change, has been associated with higher high-density lipoprotein cholesterol levels in three separate studies. Increasing evidence suggests that endothelial lipase plays a significant role in high-density lipoprotein metabolism. Endothelial lipase could be an important new target for novel therapies to raise high-density lipoprotein levels.