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Endothelial lipase is a major determinant of HDL level
Tatsuro Ishida, … , Allen D. Cooper, Thomas Quertermous
Tatsuro Ishida, … , Allen D. Cooper, Thomas Quertermous
Published February 1, 2003
Citation Information: J Clin Invest. 2003;111(3):347-355. https://doi.org/10.1172/JCI16306.
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Article Cardiology

Endothelial lipase is a major determinant of HDL level

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Abstract

A new member of the lipase gene family, initially termed endothelial lipase (gene nomenclature, LIPG; protein, EL), is expressed in a variety of different tissues, suggesting a general role in lipid metabolism. To assess the hypothesis that EL plays a physiological role in lipoprotein metabolism in vivo, we have used gene targeting of the native murine locus and transgenic introduction of the human LIPG locus in mice to modulate the level of EL expression. Evaluation of these alleles in a C57Bl/6 background revealed an inverse relationship between HDL cholesterol level and EL expression. Fasting plasma HDL cholesterol was increased by 57% in LIPG–/– mice and 25% in LIPG+/– mice and was decreased by 19% in LIPG transgenic mice as compared with syngeneic controls. Detailed analysis of lipoprotein particle composition indicated that this increase was due primarily to an increased number of HDL particles. Phospholipase assays indicated that EL is a primary contributor to phospholipase activity in mouse. These data indicate that expression levels of this novel lipase have a significant effect on lipoprotein metabolism.

Authors

Tatsuro Ishida, Sungshin Choi, Ramendra K. Kundu, Ken-ichi Hirata, Edward M. Rubin, Allen D. Cooper, Thomas Quertermous

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Figure 3

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Cholesterol levels in lipoprotein fractions obtained by FPLC. Determinat...
Cholesterol levels in lipoprotein fractions obtained by FPLC. Determination of cholesterol concentration in serum fractions obtained by FPLC revealed a correlation between LIPG genotype and HDL cholesterol levels. HDL cholesterol levels for LIPG–/– mice were significantly greater than for wild-type mice in fractions 28 and 29 (P < 0.05). HDL cholesterol levels were lower in LIPG transgenic animals for fractions 29 and 30 (P < 0.05) than in wild-type mice. KO, LIPG–/–; Tg, hLIPGTg.*P < 0.05 vs. WT.
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