Endothelial lipase is a major determinant of HDL level

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

Endogenously Produced Endothelial Lipase Enhances Binding and Cellular Processing of Plasma Lipoproteins via Heparan Sulfate Proteoglycan-mediated Pathway

“…These data further support the notion that the effects of EL on hydrolysis of lipoprotein lipids and on holoparticle uptake of lipoprotein particles are not necessarily related. These observations together with the recent in vivo studies (33,38,39) and data from Strauss et al (67), suggest that EL, through its enzymatic and structural action, may have a profound effect on HDL-mediated reverse cholesterol transport, whereas the primarily bridging effect of EL on apoB-containing lipoproteins may be more relevant for the local metabolism of these particles in the vessel wall. Additional experiments using EL knockout animals could provide more direct evidence for the relative physiological importance of enzymatic versus structural activity of EL.…”

“…As a result of EL overexpression, plasma levels of apoB-containing lipoproteins were also reduced, although to a lesser extent (33). Recent studies in EL knockout mice (38) and in mice injected with specific antibody against EL (39) provided additional evidence for a physiological importance of EL for lipid and lipoprotein metabolism in vivo.…”

ApoAV Reduces Plasma Triglycerides by Inhibiting Very Low Density Lipoprotein-Triglyceride (VLDL-TG) Production and Stimulating Lipoprotein Lipase-mediated VLDL-TG Hydrolysis

“…For example, apoAV may influence the activity of hepatic lipase and/or endothelial lipase. Although these lipolytic enzymes do not have major effects on plasma TG metabolism (27,28), they both act on HDL-phospholipids and are known to influence plasma TC levels.…”

Targeted Disruption of Endothelial Cell-selective Adhesion Molecule Inhibits Angiogenic Processes in Vitro and in Vivo

“…Cell culture, transfection, and positive and negative selection were performed as described previously (14). Genomic DNA was isolated from each clone and evaluated by Southern blot with 5Ј and 3Ј probes outside the homology domains (see Fig.…”