The role of endothelial lipase in high-density lipoprotein metabolism

• Published in: Current opinion in cardiology Vol. 19; no. 4; pp. 392 - 395
• Main Authors: Badellino, Karen O, Rader, Daniel J
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins, Inc 01-07-2004
• Subjects: Animals; Apolipoprotein A-I - genetics; Apolipoprotein A-I - metabolism; Arteriosclerosis - enzymology; Arteriosclerosis - prevention & control; Biological Transport; Cholesterol, HDL - genetics; Cholesterol, HDL - metabolism; Humans; Lipase - antagonists & inhibitors; Lipase - genetics; Lipase - physiology; Lipoproteins, HDL - genetics; Lipoproteins, HDL - metabolism; Mice
• ISSN: 0268-4705; 1531-7080
• DOI: 10.1097/01.hco.0000130161.89169.02

PURPOSE OF REVIEWElevating 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.
RECENT FINDINGSInhibition 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.
SUMMARYIncreasing 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.