Ma_2003_Proc.Natl.Acad.Sci.U.S.A_100_2748

Reference

Title : Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism - Ma_2003_Proc.Natl.Acad.Sci.U.S.A_100_2748
Author(s) : Ma K , Cilingiroglu M , Otvos JD , Ballantyne CM , Marian AJ , Chan L
Ref : Proc Natl Acad Sci U S A , 100 :2748 , 2003
Abstract :

High-density lipoprotein (HDL) protects against atherosclerosis. Endothelial lipase (EL) has been postulated to be involved in lipoprotein, and possibly HDL, metabolism, yet the evidence has been scarce and conflicting. We have inactivated EL in mice by gene targeting. EL(-/-) mice have elevated plasma and HDL cholesterol, and increased apolipoproteins A-I and E. NMR analysis reveals an abundance of large HDL particles. There is down-regulation of the transcripts for phospholipid transfer protein, but up-regulation of those for hepatic lipase and lipoprotein lipase. Plasma lecithin:cholesterol acyltransferase is unchanged despite an increase in hepatic mRNA; lecithin:cholesterol acyltransferase activity toward endogenous EL(-/-) substrate is, however, reduced by 50%. HDL clearance is decreased in EL(-/-) mice; both the structure of HDL and the presence of EL are factors that determine the rate of clearance. To determine EL's role in humans, we find a significant association between a single-nucleotide polymorphism 584C/T in the EL (LIPG) gene and HDL cholesterol in a well characterized population of 372 individuals. We conclude that EL is a major determinant of HDL concentration, structure, and metabolism in mice, and a major determinant of HDL concentration in humans.

PubMedSearch : Ma_2003_Proc.Natl.Acad.Sci.U.S.A_100_2748
PubMedID: 12601178
Gene_locus related to this paper: human-LIPG

Related information

Mutation T111I_human-LIPG
Gene_locus human-LIPG

Citations formats

Ma K, Cilingiroglu M, Otvos JD, Ballantyne CM, Marian AJ, Chan L (2003)
Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism
Proc Natl Acad Sci U S A 100 :2748

Ma K, Cilingiroglu M, Otvos JD, Ballantyne CM, Marian AJ, Chan L (2003)
Proc Natl Acad Sci U S A 100 :2748