J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M600036-JLR200 on July 30, 2006

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Journal of Lipid Research, Vol. 47, 2191-2197, October 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Endothelial lipase is less effective at influencing HDL metabolism in vivo in mice expressing apoA-II

Uli C. Broedl1,*,{dagger}, Weijun Jin*, Ilia V. Fuki*, John S. Millar* and Daniel J. Rader*

* Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA
{dagger} Department of Internal Medicine II, University of Munich, Munich, Germany

Published, JLR Papers in Press, July 30, 2006.

1 To whom correspondence should be addressed. e-mail: uli.broedl{at}med.uni-muenchen.de

Endothelial lipase (EL) plays an important physiological role in modulating HDL metabolism. Data suggest that plasma contains an inhibitor of EL, and previous studies have suggested that apolipoprotein A-II (apoA-II) inhibits the activity of several enzymes involved in HDL metabolism. Therefore, we hypothesized that apoA-II may reduce the ability of EL to influence HDL metabolism. To test this hypothesis, we determined the effect of EL expression on plasma phospholipase activity and HDL metabolism in human apoA-I and human apoA-I/A-II transgenic mice. Expression of EL in vivo resulted in lower plasma phospholipase activity and significantly less reduction of HDL-cholesterol, phospholipid, and apoA-I levels in apoA-I/A-II double transgenic mice compared with apoA-I single transgenic mice. We conclude that the presence of apoA-II on HDL particles inhibits the ability of EL to influence the metabolism of HDL in vivo.

Supplementary key words high density lipoprotein metabolism • apolipoprotein A-II • high density lipoprotein containing apolipoprotein A-I but no apolipoprotein A-II • high density lipoprotein containing both apolipoprotein A-I and apolipoprotein A-II • transgenic mice

Abbreviations: AdGFP, adenovirus encoding green fluorescent protein; AdhEL, adenovirus encoding human endothelial lipase; apoA-I, apolipoprotein A-I; DPPC, dipalmitoylphosphatidylcholine; EL, endothelial lipase; HDL-C, high density lipoprotein-cholesterol; HSPG, heparan sulfate proteoglycan; LpA-I, high density lipoprotein containing apolipoprotein A-I but no apolipoprotein A-II; LpA-I/A-II, high density lipoprotein containing both apolipoprotein A-I and apolipoprotein A-II


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