A novel endothelial-derived lipase that modulates HDL metabolism

Abstract

High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease. At least 50% of the variation in HDL cholesterol levels is genetically determined, but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family, both influence HDL metabolism and the HL (LIPC) locus has been associated with variation in HDL cholesterol levels in humans. We describe here the cloning and in vivo functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells in vitro and thus has been termed endothelial lipase (encoded by the LIPG gene). EL is expressed in vivo in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and in vivo effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology.

Putative Role of Endothelial Lipase in Dialysis Patients with Hypoalbuminemia and Inflammation

“…Endothelial lipase (EL) is a newly discovered member of the triacylglycerol lipase family, which was cloned by subtractive hybridization in cultured human umbilical vein endothelial cells undergoing tube formation [10, 11]. The sequence of EL is similar to that of hepatic lipase and lipoprotein lipase.…”

Human skeletal muscle perilipin 2 and 3 expression varies with insulin sensitivity

“…It is not possible to link this to higher intramuscular diacylglycerol content and/or higher intramuscular long chain fatty acid content, and thus provide a possible mechanism for the lower insulin sensitivity. Endothelial lipase expressionis possibly involved in HDL-particle catabolism [32][33][34], but in human skeletal muscle the role of endothelial lipase is largely unknown.…”

Endothelial Lipase: A Novel Drug Target for HDL and Atherosclerosis?

“…In 1999, a gene encoding endothelial lipase was reported as a new member of the triglyceride lipase gene family [3,4]. This gene was cloned simultaneously by two different groups using two different strategies.…”

“…This gene was cloned simultaneously by two different groups using two different strategies. Jaye et al [3] exposed the monocyte cell line, THP-1, to oxidized LDL-C after differentiation with phorbol 12-myristate 13-acetate (PMA). An RNA amplification product was found in the oxidized LDL-treated cells but not in untreated cells.…”

“…The cDNA that was upregulated in the early stages of tube formation was found to be a lipase with significant sequence identity with hepatic lipase and lipoprotein lipase. [3]. The structure was based on the crystal structure of pancreatic lipase [5] and a published molecular model of lipoprotein lipase [7].…”