Effects of genotype and diet on cholesterol efflux into plasma and lipoproteins of normal, apolipoprotein A-I-, and apolipoprotein E-deficient mice.
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-beta-migrating VLDL as well as in HDL-like lipoproteins, which have either electrophoretic alpha- or gamma-mobilities. The latter particle resembled gamma-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 gamma-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 gamma-LpE and partially because of the contribution of apoE-containing lipoproteins to esterification of cholesterol in plasma.
Huang
Y
Y
Institut für Arterioskleroseforschung, Universität Münster, Germany.
Zhu
Y
Y
Langer
C
C
Raabe
M
M
Wu
S
S
Wiesenhütter
B
B
Seedorf
U
U
Maeda
N
N
Assmann
G
G
von Eckardstein
A
A
D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency*; D001057:Apolipoproteins E / Q000172:deficiency*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D004032:Diet; D004586:Electrophoresis; D005838:Genotype; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008074:Lipoproteins; D002784:Cholesterol