High-density lipoproteins from human alcoholics exhibit impaired reverse cholesterol transport function

We have previously shown that chronic alcohol consumption leads to inhibiti on of sialylation of apolipoprotein E (apo E) that results in its impaired binding to high-density lipoprotein (HDL) molecule. Because apo E plays a m ajor role in reverse cholesterol transport (RCT), we speculated that ethano l-mediated formation of HDL molecules without apo E may affect the RCT proc ess. Therefore, we have investigated whether the RCT function of HDL is aff ected in chronic alcoholics with or without liver disease compared with non drinkers. HDL was isolated from fasting plasma of normal subjects, n = 9 (n ondrinkers), chronic alcoholics, n = 8 (ALC), and chronic alcoholics with l iver disease, n = 6 (ALD). A portion of HDL sample from each subject was ev aluated for its cholesterol efflux capacity from [H-3]cholesterol oleate pr eloaded mouse macrophages. The remaining portion of each HDL sample was lab eled with [H-3]cholesterol oleate and evaluated for its ability to deliver cholesterol to the river using HepG2 cells in culture. Cholesterol efflux c apacity of HDLs was decreased by 83% (P < .0002) in alcoholics without live r disease and by 84% (P < .0006) in alcoholics with liver disease compared with the HDLs from nondrinkers. The capacities of HDLs to deliver cholester ol to the river were decreased by 54% (P < .005) in alcoholics without live r disease and by 54% (P < .005) in alcoholics with liver disease compared w ith the HDLs from nondrinkers. The fact that further complications by liver disease in alcoholic subjects did not significantly exacerbate the extent of impairment in RCT function of HDL suggest that alcohol per se is respons ible for its deleterious effects on RCT. Significantly, plasma HDL apo E co ncentration relative to that of apo A1 (apo E/apo A1 ratio) was also decrea sed by 31% to 32% (P < .0005) in alcoholics without or with liver disease c ompared with nondrinkers. It is therefore concluded that chronic alcohol co nsumption adversely affects the RCT function of HDL by altering its associa tion with apo E due to ethanol-induced desialylation of apo E. Copyright (C ) 2000 by W.B. Saunders Company.