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Originally published In Press as doi:10.1194/jlr.M400212-JLR200 on February 1, 2005

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Journal of Lipid Research, Vol. 46, 896-903, May 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Evidence that endothelial lipase remodels high density lipoproteins without mediating the dissociation of apolipoprotein A-I

A. Jahangiri1,*, D. J. Rader{dagger}, D. Marchadier{dagger}, L. K. Curtiss§, D. J. Bonnet§ and K-A. Rye*,**,{dagger}{dagger}

* Lipid Research Group, Heart Research Institute, Camperdown, Sydney, New South Wales 2050, Australia
{dagger} Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
§ Department of Immunology, Scripps Research Institute, La Jolla, CA 92037
** Department of Medicine, University of Sydney, Sydney, New South Wales 2006, Australia
{dagger}{dagger} Department of Medicine, University of Melbourne, Melbourne, Victoria 3010, Australia

1 To whom correspondence should be addressed. e-mail: a.jahangiri{at}hri.org.au

Endothelial lipase (EL) is a triglyceride lipase gene family member that has high phospholipase and low triglyceride lipase activity. The aim of this study was to determine whether the phospholipase activity of EL is sufficient to remodel HDLs into small particles and mediate the dissociation of apolipoprotein A-I (apoA-I). Spherical, reconstituted HDLs (rHDLs) containing apoA-I only [(A-I)rHDLs], apoA-II only [(A-II)rHDLs], or both apoA-I and apoA-II [(A-I/A-II) rHDLs] were prepared. The rHDLs, which contained only cholesteryl esters in their core and POPC on the surface, were incubated with EL. As the rHDLs did not contain triacylglycerol, only the POPC was hydrolyzed. Hydrolysis was greater in the (A-I/A-II)rHDLs than in the (A-I)rHDLs. The (A-II)rHDL phospholipids were not hydrolyzed by EL. EL remodeled the (A-I)rHDLs and (A-I/A-II)rHDLs, but not the (A-II)rHDLs, into smaller particles. The reduction in particle size was related to the amount of phospholipid hydrolysis, with the diameter of the (A-I/A-II)rHDLs decreasing more than that of the (A-I)rHDLs. These changes did not affect the conformation of apoA-I, and neither apoA-I nor apoA-II dissociated from the rHDLs. Comparable results were obtained when human plasma HDLs were incubated with EL.

These results establish that the phospholipase activity of EL remodels plasma HDLs and rHDLs into smaller particles without mediating the dissociation of apolipoproteins.

Abbreviations: apoA-I, apolipoprotein A-I; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; EL, endothelial lipase; RAM-Fc, rabbit anti-mouse Fc; rHDL, reconstituted high density lipoprotein; TG, triacylglycerol; UC, unesterified cholesterol

Supplementary key words phospholipids • hydrolysis • lipoprotein metabolism


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