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 lipo-proteins (HDL) which contain either apolipoprotein (apo) A-I or apoE as their only apolipoproteins. From these initial acceptors, which are termed pre/,3-LpA-I and y-LpE, re-spectively, cell-derived cholesterol is transferred to LDL via the bulk ofHDL termed c-LpA-I. In this study we analyzed the effect in plasma of the genetically determined apoE poly-morphism on the formation of-y-LpE, uptake and transfer of cell-derived cholesterol to LDL. y-LpE was immunologi-cally detectable in plasmas of individuals carrying at least one apoE3-allele but not in apoE3-free plasmas. During one minute incubation with [3HJcholesterol-labeled fibroblasts, y-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, respec-tively. 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 a-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. (J. Clin. Invest. 1995. 96:2693-2701.) Key words: HDL-subclasses * reverse cholesterol transport * arterioscle-rosi