Cholesterol net transport, esterification, and transfer in human hyperlipidemic plasma.

Abstract

Cholesterol esterification, cholesteryl ester transfer between lipoproteins, and cholesterol transport between lipoproteins and cultured cells have been measured in the plasma of 22 patients with primary hyperlipidemia and 10 normolipidemic subjects. In hyperbetalipoproteinemia, increase in plasma low density lipoprotein levels was associated with a reduction of cholesteryl ester transfer rates, and with a reversal of the normal direction of sterol transport between fibroblasts and their plasma culture medium. Instead of net transport from cells to medium there was a net uptake of sterol from plasma by the cells, despite a level of plasma lecithin/cholesterol acyltransferase activity that was within the normal range. In dysbetalipoproteinemia, esterification rates were increased above normal levels, but cholesteryl ester transfer was reduced and the direction of sterol transport between the cells and plasma medium was reversed, as in the hyperbetalipoproteinemic group. In hypertriglyceridemia, those subjects with cardiovascular disease showed a metabolic pattern similar to the hyperbetalipoproteinemic group. The subjects in this group without symptoms of cardiovascular disease showed a normal direction of sterol transport, normal or raised rates of cholesteryl ester transfer between lipoproteins, and an increased rate of sterol esterification in plasma that decreased towards normal levels as plasma triglyceride levels decreased. Despite their quite distinct metabolic patterns there was no consistent difference between the two hypertriglyceridemic groups in triglyceride or cholesterol levels, very low density lipoprotein composition, or electrophoretic or isoelectric focussing patterns. All hypertriglyceridemic subjects with documented cardiovascular disease showed reversed cell-plasma sterol transport and all subjects without such disease showed a normal direction of cell-plasma sterol transport. The results of this study indicate major and reproducible abnormalities in plasma cholesterol metabolism in several groups of subjects with genetically distinct hyperlipidemias, who are at risk for atherosclerotic vascular disease. The possible predictive value of sterol metabolic measurements in the analysis of cardiovascular disease is discussed.