Effects of the apolipoprotein E polymorphism on uptake and transfer of cell-derived cholesterol in plasma.
The reverse cholesterol transport is initiated by the uptake of cholesterol into minor subfractions of high density lipoproteins (HDL) which contain either apolipoprotein (apo) A-I or apoE as their only apolipoproteins. From these initial acceptors, which are termed prebeta1-LpA-I and gamma-LpE, respectively, cell-derived cholesterol is transferred to LDL via the bulk of HDL termed alpha-LpA-I. In this study we analyzed the effect in plasma of the genetically determined apoE polymorphism on the formation of gamma-LpE, uptake and transfer of cell-derived cholesterol to LDL. Gamma-LpE was immunologically detectable in plasmas of individuals carrying at least one apoE3-allele but not in apoE3-free plasmas. During one minute incubation with [3H]cholesterol-labeled fibroblasts, gamma-LpE of plasmas from apoE3/3 subjects accumulated 7 and 13-fold more radioactivity than the respective fractions in plasmas from apoE2/2- and apoE4/4-subjects, respectively. Totally, 30% less [3H]cholesterol was released into plasmas of apoE2/2 and apoE4/4-individuals as compared with plasmas of apoE3/3-subjects. Moreover, plasmas of apoE3/3 individuals accumulated 50% and 65% more cell-derived [3H]cholesterol in alpha-LpA-I2 than plasmas of apoE4/4 and apoE2/2-subjects, respectively. These results indicate that the apoE-polymorphism is an important determinant of the uptake and transfer of cell-derived cholesterol in plasma.
Huang
Y
Y
Institut für Arterioskleroseforschung an der Universität Münster, Federal Republic of Germany.
von Eckardstein
A
A
Wu
S
S
Assmann
G
G
D016632:Apolipoprotein A-I / Q000302:isolation & purification; D001053:Apolipoproteins / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D012867:Skin / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase; D014280:Triglycerides / Q000097:blood; D010738:Type C Phospholipases
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase