A CELL-CULTURE SYSTEM FOR SCREENING HUMAN SERUM FOR ABILITY TO PROMOTE CELLULAR CHOLESTEROL EFFLUX - RELATIONS BETWEEN SERUM COMPONENTS ANDEFFLUX, ESTERIFICATION, AND TRANSFER

A cell culture system was employed to test a large number of samples o f human serum for the ability to stimulate the efflux of cell choleste rol. The extent of efflux obtained with each specimen was correlated w ith the serum concentrations of cholesterol, triglycerides, apoprotein (ape) B, apo A-I, apo A-II, and lipoprotein subfractions (ie, high-de nsity lipoprotein(2) [HDL(2)], HDL(3), lipoprotein [Lp] A-I, and LpA-I :A-II). In addition, the subsequent esterification of the released cho lesterol and the distribution of the synthesized exogenous cholesteryl esters between HDL and low-density lipoprotein/very-low-density lipop rotein provided estimates of the lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities of ea ch serum. The values for these activities were analyzed for correlatio ns with cell efflux and the various serum parameters. Cell cholesterol efflux best correlated with serum total HDL cholesterol values. HDL(2 ) and HDL(3) correlated about equally well with efflux, whereas LpA-I demonstrated a much greater association with efflux than did LpA-I:A-I I, Analysis of the data by partial correlation analysis indicated that HDL(3) and LpA-I were the HDL subfractions most closely associated wi th efflux. Esterification of the released radiolabeled cholesterol was strongly and positively correlated with serum triglyceride concentrat ions and negatively related to the serum concentrations of HDL(2). The re was no relation between esterification values, which reflect LCAT a ctivity, and efflux. The transfer of the labeled cholesteryl esters be tween HDL and apoB-containing lipoproteins was used as a measure of CE TP activity and demonstrated a pattern in which all apoB-related param eters were positively correlated to transfer of esterified cholesterol , and all HDL associated parameters, particularly HDL(3), were negativ ely related to transfer. No relations were observed between efflux, es terification, and transfer.