The role of endothelial lipase in high-density lipoprotein metabolism

被引:29
作者
Badellino, KO
Rader, DJ
机构
[1] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA
关键词
endothelial lipase; high density lipoprotein; phospholipids; single-nucleotide polymorphisms;
D O I
10.1097/01.hco.0000130161.89169.02
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Purpose of review 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, apoAl, 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 findings 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. Summary 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.
引用
收藏
页码:392 / 395
页数:4
相关论文
共 23 条
[1]
Immunohistochemical localization of endothelial cell-derived lipase in atherosclerotic human coronary arteries [J].
Azumi, H ;
Hirata, K ;
Ishida, T ;
Kojiam, Y ;
Rikitake, Y ;
Takeuchi, S ;
Inoue, N ;
Kawashima, S ;
Hayashi, Y ;
Itoh, H ;
Quertermous, T ;
Yokoyama, M .
CARDIOVASCULAR RESEARCH, 2003, 58 (03) :647-654
[2]
BROEDL U, 2004, IN PRESS CIRC RES
[3]
Effects of nonlipolytic ligand function of endothelial lipase on high density lipoprotein metabolism in vivo [J].
Broedl, UC ;
Maugeais, C ;
Marchadier, D ;
Glick, JM ;
Rader, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (42) :40688-40693
[4]
Endothelial lipase: a new lipase on the block [J].
Choi, SY ;
Hirata, K ;
Ishida, T ;
Quertermous, T ;
Cooper, AD .
JOURNAL OF LIPID RESEARCH, 2002, 43 (11) :1763-1769
[5]
Identification of genetic variants in endothelial lipase in persons with elevated high-density lipoprotein cholesterol [J].
deLemos, AS ;
Wolfe, ML ;
Long, CJ ;
Sivapackianathan, R ;
Rader, DJ .
CIRCULATION, 2002, 106 (11) :1321-1326
[6]
Endogenously produced endothelial lipase enhances binding and cellular processing of plasma lipoproteins via heparan sulfate proteoglycan-mediated pathway [J].
Fuki, IV ;
Blanchard, N ;
Jin, WJ ;
Marchadier, DHL ;
Millar, JS ;
Glick, JM ;
Rader, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (36) :34331-34338
[7]
High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype [J].
Halverstadt, A ;
Phares, DA ;
Ferrell, RE ;
Wilund, KR ;
Goldberg, AP ;
Hagberg, JM .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2003, 52 (11) :1505-1511
[8]
Regulated expression of endothelial cell-derived lipase [J].
Hirata, K ;
Ishida, T ;
Matsushita, H ;
Tsao, PS ;
Quertermous, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 272 (01) :90-93
[9]
Cloning of a unique lipase from endothelial cells extends the lipase gene family [J].
Hirata, K ;
Dichek, HL ;
Cioffi, JA ;
Choi, SY ;
Leeper, NJ ;
Quintana, L ;
Kronmal, GS ;
Cooper, AD ;
Quertermous, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (20) :14170-14175
[10]
Ishida T, 2003, J CLIN INVEST, V111, P347, DOI [10.1172/JCI200316306, 10.1172/JCI16306]