Relation of High-Density Lipoprotein Charge Heterogeneity, Cholesterol Efflux Capacity, and the Expression of High-Density Lipoprotein-Related Genes in Mononuclear Cells to the HDL-Cholesterol Level.

The heterogeneity and content of human plasma high-density lipoprotein (HDL) related to their atheroprotective properties determined by various molecular and cellular mechanisms still remain to be completely clarified. For 29 atherosclerosis-free male subjects, we studied the relationship of plasma lipid levels and the content of apolipoprotein A-I (apoA-I)-containing HDL with pre-electrophoretic mobility, the efficiency of BODIPY-cholesterol efflux from RAW 264.7 macrophages to apolipoprotein B (apoB)-deficient plasma, and the expression level of 22 genes related to HDL metabolism in mononuclear cells. A significant decrease in the absolute content of apoA-I in pre-HDL was found in subjects with hypoalphalipoproteinemia compared with the subjects with hyperalphalipoproteinemia. The pre-to--ratio of the apoA-I content was constant within the HDL-cholesterol (HDL-C) range 0.59 to 2.24mM. However, this ratio was significantly increased with an increase in the plasma triacylglycerol (TAG) content from 0.59 to 3.42mM. A correlation of the level of pre-HDL with the basal and ABCA1-mediated efflux of cholesterol is shown. The transcript levels for six HDL-metabolizing genes (LDLR, LCAT, ABCA1, SCARB1, ZDHHC8, and BMP1) were decreased, while the transcript level of APOA1 gene was increased in mononuclear cells of subjects with hyperalphalipoproteinemia as compared with subjects with hypoalphalipoproteinemia. A reduction of the intracellular cholesterol level and inhibition of the expression of cholesterol transporters by nascent HDL in mononuclear cells from subjects with hyperalphalipoproteinemia are suggested. Hyperalphalipoproteinemia can be a driving force of the decreased flux of cholesteryl ester to the liver and the increased TAG hydrolysis. The atheroprotective effect of pre-HDL in hypertriglyceridemia is proposed.