Endothelial lipase is less effective at influencing HDL metabolism in vivo in mice expressing apoA-II.
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.
Broedl
Uli C
UC
Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. uli.broedl@med.uni-muenchen.de
Jin
Weijun
W
Fuki
Ilia V
IV
Millar
John S
JS
Rader
Daniel J
DJ
D000256:Adenoviridae; D000818:Animals; D016633:Apolipoprotein A-II / Q000378:metabolism*; D015153:Blotting, Western; D005822:Genetic Vectors; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D014162:Transfection
D016633:Apolipoprotein A-II; D008075:Lipoproteins, HDL; C410382:LIPG protein, human; D008049:Lipase