Nature Genetics
21, 424 - 428 (1999)
doi:10.1038/7766
A novel endothelial-derived lipase that modulates HDL metabolismMichael Jaye2, Kevin J. Lynch2, John Krawiec2, Dawn Marchadier1, Cyrille Maugeais1, Kim Doan2, Victoria South2, Dilip Amin2, Mark Perrone2
& Daniel J. Rader11
Department of Medicine, University of Pennsylvania
Health System, Philadelphia, Pennsylvania
19104-6100, USA. 2
Cardiovascular Biology Department, Rhone-Poulenc Rorer
Research and Development, Collegeville, Pennsylvania
19426-0107, USA.
Correspondence should be addressed to Daniel J. Rader rader@mail.med.upenn.eduHigh-density lipoprotein (HDL) cholesterol levels are inversely associated
with risk of atherosclerotic cardiovascular disease1. At least
50% of the variation in HDL cholesterol levels is genetically determined2,
3, 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 metabolism2,
4,
5,
6 and the HL (LIPC) locus has been associated with
variation in HDL cholesterol levels in humans7,
8. 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.
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