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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2010-2019.)
© 1997 American Heart Association, Inc.

Articles

Effects of Genotype and Diet on Cholesterol Efflux into Plasma and Lipoproteins of Normal, Apolipoprotein A-I-, and Apolipoprotein E-Deficient Mice

Yadong Huang; Yanhong Zhu; Claus Langer; Martin Raabe; Shili Wu; Bernd Wiesenhütter; Udo Seedorf; Nobuyo Maeda; Gerd Assmann; ; Arnold von Eckardstein

From the Institut für Arterioskleroseforschung an der Universität Münster, Münster, Germany (Y.H., Y.Z., M.R., S.W., B.W., U.S., G.A., A.v.E.); the Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westfälische Wilhelms-Universität Münster, Münster, Germany (C.L., G.A., A.v.E.); and the Department of Pathology and Curriculum in Genetics and of the Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina (N.M.).

Correspondence to Dr. Arnold von Eckardstein, Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany.

Abstract We investigated the contribution of apoE to cholesterol efflux into plasmas of normal, apoA-I-, and apoE-deficient mice, which were fed with chow- and cholesterol-rich diets. Plasmas of normal and apoA-I-deficient mice contain apoE in pre-ß-migrating VLDL as well as in HDL-like lipoproteins, which have either electrophoretic - or -mobilities. The latter particle resembled -LpE in human plasma also by its mobility on nondenaturing two-dimensional electrophoresis. No apoE-containing lipoproteins were found in plasmas of apoE-deficient mice. When apoA-I- and apoE-deficient mice received both chow- and fat-rich diets, their plasmas released significantly less ³H-cholesterol from radiolabeled fibroblasts than did plasma of normal mice. Removal of apoE from plasmas of normal and apoA-I-deficient mice by anti-apoE immunoaffinity chromatography decreased their cholesterol efflux capacities (per 1 minute/per 1 hour) by 26%/40% (P=0.0092/0.0007) and 30%/26% (P=0.0092/0.0003), respectively. Net cholesterol efflux from fibroblasts into apoA-I-deficient plasma was 45% lower compared with plasma of normal mice. Incubation of fibroblasts with apoE-deficient plasma caused net influx of cholesterol. Prior addition of human apoE to or removal of apoB-containing lipoproteins from apoE-deficient plasma restored its ability to cause net cholesterol efflux to 50% of normal plasma. Some of the differences between cholesterol efflux into normal and apoE-deficient plasmas were attributable to the failure of apoE-deficient plasmas to take up cell-derived ³H-cholesterol into -LpE. Compared with normal plasma, both apoA-I-deficient and apoE-deficient plasmas were significantly decreased in their activity to esterify cell-derived ³H-cholesterol. Anti-apoE chromatography decreased significantly cholesterol esterification in normal plasma and apoA-I-deficient plasma but not in apoE-deficient plasma. Taken together, the data provide evidence that apoE is an important contributor to reverse cholesterol transport, partially because of initial uptake of cell-derived cholesterol by -LpE and partially because of the contribution of apoE-containing lipoproteins to esterification of cholesterol in plasma.

Key Words: reverse cholesterol transport • HDL subclasses • atherosclerosis • animal models

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