Altered reverse cholesterol transport function of HDL in hypercholesterolemic human model

Human plasma HDL apolipoproteins (Apo) A, E and recently discovered ApoJ play crucial roles in cholesterol clearance via the reverse cholesterol transport (RCT) process. We have previously shown structural alterations of HDL apoproteins in hypercholesterolemic obese rats. The functional implications of these alterations remain unclear.The present study explores the physiological alterations, if any, in HDL function in hypercholesterolemic humans. Blood samples of hypercholesterolemic subjects(N=10, plasma cholesterol >240 mg/dl) and normal cholesterol controls(N=10, plasma cholesterol <200 mg/dl) were collected and processed for HDL preparation by established standard protocols. For efflux studies on RCT.Iabeled cholesterol-laden human monocyte macrophages were individually incubated with HDL3 fractions in a serum free medium and the radioactivities of the secreted cholesterol determined. For hepatic uptake studies, cholesterol-labeled HDL, fractions were individually incubated with Hep G-2 cells in Krebs buffer and the radioactivities of the cholesterol taken up by the cells determined. Results: Decreases of 32.5% (p<0.05 ) and 40.45 (p<0.001), respectively, in the efflux and uptake of cholesterol were seen in hypercholesterolemic group compared to controls. Conclusion: The functional ability of HDL with regard to RCT is impaired in hypercholesterolemia. This might have led to a substantial defect in the cholesterol clearance in these subjects. The relevance of these findings may be crucial to our understanding of hypercholesterolemia and cardiovascular diseases in humans. (Supported in part by a grant BP/97-PG-03 from BioProbes, Inc. Gaithersburg. MD).