High-density lipoproteins from human alcoholics exhibit impaired reverse cholesterol transport function.
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.
Rao
M N
MN
DVA Medical Center and The Department of Medicine, The George Washington University, Washington, DC, USA.
Liu
Q H
QH
Marmillot
P
P
Seeff
L B
LB
Strader
D B
DB
Lakshman
M R
MR
D000328:Adult; D000437:Alcoholism / Q000097:blood*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000097:blood*; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000502:physiology; D008297:Male; D051379:Mice; D008875:Middle Aged
D008075:Lipoproteins, HDL; D002784:Cholesterol