The role of endothelial lipase in high-density lipoprotein metabolism.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Badellino
Karen O
KO
School of Nursing, University of Pennsylvania, Philadelphia 19104, USA.
Rader
Daniel J
DJ
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D001161:Arteriosclerosis / Q000201:enzymology* / Q000517:prevention & control; D001692:Biological Transport; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D051379:Mice
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; C410382:LIPG protein, human; D008049:Lipase; C498741:Lipg protein, mouse