We have previously shown that chronic alcohol consumption leads to inhibition of sialylation of
apolipoprotein E (
apo E) that results in its impaired binding to
high-density lipoprotein (HDL) molecule. Because
apo E plays a major role in reverse
cholesterol transport (RCT), we speculated that
ethanol-mediated formation of HDL molecules without
apo E may affect the RCT process. Therefore, we have investigated whether the RCT function of HDL is affected in chronic alcoholics with or without
liver disease compared with nondrinkers. HDL was isolated from fasting plasma of normal subjects, n = 9 (nondrinkers), chronic alcoholics, n = 8 (ALC), and chronic alcoholics with
liver disease, n = 6 (ALD). A portion of HDL sample from each subject was evaluated for its
cholesterol efflux capacity from [3H]
cholesterol oleate preloaded mouse macrophages. The remaining portion of each HDL sample was labeled with [3H]
cholesterol oleate and evaluated for its ability to deliver
cholesterol to the liver using HepG2 cells in culture.
Cholesterol efflux capacity of HDLs was decreased by 83% (P < .0002) in alcoholics without
liver disease and by 84% (P < .0006) in alcoholics with
liver disease compared with the HDLs from nondrinkers. The capacities of HDLs to deliver
cholesterol to the liver were decreased by 54% (P < .005) in alcoholics without
liver disease and by 64% (P < .005) in alcoholics with
liver disease compared with 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 responsible for its deleterious effects on RCT. Significantly, plasma
HDL apo E concentration relative to that of
apo A1 (
apo E/
apo A1 ratio) was also decreased by 31% to 32% (P < .0005) in alcoholics without or with
liver disease compared with nondrinkers. It is therefore concluded that chronic alcohol consumption adversely affects the RCT function of HDL by altering its association with
apo E due to
ethanol-induced desialylation of
apo E.