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Journal of Lipid Research, Vol. 44, 884-892, May 2003
Copyright © 2003 by Lipid Research, Inc.

Structural and functional properties of human plasma high density-sized lipoprotein containing only apoE particles

Larbi Krimbou^*, Michel Marcil^*, Hitoshi Chiba and Jacques Genest, Jr.^1,*

^* Cardiovascular Genetics Laboratory, McGill University Health Center/Royal Victoria Hospital, Montréal, Québec H3A 1A1, Canada
Department of Laboratory Medicine, Hokkaido University School of Medicine, North-14, West-5, Sapporo 060-8648, Japan

¹ To whom correspondence should be addressed. e-mail: jacques.genest{at}muhc.mcgill.ca

To investigate the metabolism of HDL-apolipoprotein E (apoE) particles in human plasma, we isolated a fraction of plasma HDL-apoEs that lack apoA-I (HDL-LpE) from subjects with apoE3/3 phenotype by immunoaffinity. Plasma HDL-LpE had a particle size ranging from 9 nm to 18.5 nm in diameter and was characterized by two-dimensional nondenaturing gradient gel electrophoresis as having either -, preß₁-, preß₂-, or -electrophoretic mobility. HDL-LpE was also present in the medium of cultured human hepatoma cell lines and monocyte-derived macrophages. The majority of apoE3 was found as a monomeric form in HDL-LpE and floated at density d > 1.21 g/ml. Plasma levels of HDL-LpE in normolipidemic, CETP-deficient, and ABCA1-deficient subjects were 0.72 ± 0.15 mg/dl (n = 12), 1.77 ± 0.75 mg/dl (n = 3), and 0.55 ± 0.11 mg/dl (n = 3), respectively. The ratio of HDL-apoE containing apoA-I to HDL-LpE was significantly higher 4 h after a fat load, representing a 35 ± 9% increase (n = 3). Isolated plasma HDL-LpE3 was as effective as apoE3, reconstituted HDL particles, or apoA-I in promoting cellular cholesterol efflux.

These results demonstrate that 1) plasma HDL-LpE may have hepatogenous and macrophagic origins; 2) HDL-LpE was preserved even with large reductions in apoA-I-containing lipoproteins; 3) HDL-LpE was active in the transfer of apoE to triglyceride-rich lipoproteins, and 4) HDL-LpEs efficiently take up cell-derived cholesterol.

Abbreviations: ABCA1, ATP binding cassette A1; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; LpE, lipoprotein containing only apoE; PEG, polyethylene glycol; RCT, reverse cholesterol transport; TD, Tangier disease; TRL, triglyceride-rich lipoprotein; 2D-PAGGE, two-dimensional nondenaturing gradient gel electrophoresis

Supplementary key words HDL-apoE • hypoalphalipoproteinemia • postprandial lipemia • cholesterol efflux • reverse cholesterol transport

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