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Journal of Lipid Research, Vol. 49, 115-126, January 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Remodeling of apolipoprotein E-containing spherical reconstituted high density lipoproteins by phospholipid transfer protein

Nongnuch Settasatian^1,*, Philip J. Barter^*, and Kerry-Anne Rye^2,*,,

^* Lipid Research Group, Heart Research Institute, Sydney, New South Wales 2050, Australia
Faculty of Medicine, University of Sydney, Sydney, New South Wales 2006, Australia
Department of Medicine, University of Melbourne, Melbourne, Victoria 3010, Australia

Published, JLR Papers in Press, October 5, 2007.

¹ Present address of N. Settasatian: Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.

² To whom correspondence should be addressed. e-mail: ryek{at}hri.org.au

Phospholipid transfer protein (PLTP) transfers phospholipids between HDL and other lipoproteins in plasma. It also remodels spherical, apolipoprotein A-I (apoA-I)-containing HDL into large and small particles in a process involving the dissociation of lipid-free/lipid-poor apoA-I. ApoE is another apolipoprotein that is mostly associated with large, spherical HDL that do not contain apoA-I. Three isoforms of apoE have been identified in human plasma: apoE2, apoE3, and apoE4. This study investigates the remodeling of spherical apoE-containing HDL by PLTP and the ability of PLTP to transfer phospholipids between apoE-containing HDL and phospholipid vesicles. Spherical reconstituted high density lipoproteins (rHDL) containing apoA-I [(A-I)rHDL], apoE2 [(E2)rHDL], apoE3 [(E3)rHDL], or apoE4 [(E4)rHDL] as the sole apolipoprotein were prepared by incubating discoidal rHDL with low density lipoproteins and lecithin:cholesterol acyltransferase. PLTP remodeled the spherical, apoE-containing rHDL into large and small particles without the dissociation of apoE. The PLTP-mediated remodeling of apoE-containing rHDL was more extensive than that of (A-I)rHDL. PLTP transferred phospholipids from small unilamellar vesicles to apoE-containing rHDL in an isoform-dependent manner, but at a rate slower than that for spherical (A-I)rHDL. It is concluded that apoE enhances the capacity of PLTP to remodel HDL but reduces the ability of HDL to participate in PLTP-mediated phospholipid transfers.

Supplementary key words high density lipoprotein fusion • phospholipid transfers • HDL metabolism

Abbreviations: apoE, apolipoprotein E; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; DPPC, 1,2-dipalmitoyl L-3-phosphatidylcholine; PLTP, phospholipid transfer protein; rHDL, reconstituted high density lipoprotein; UC, unesterified cholesterol

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