The effect of apolipoprotein (apo) E phenotype on the concentration and chemical composition of plasma lipoproteins was studied in 73 male alcohol abusers and 50 male controls. The apo E phenotype was confirmed by genotyping to avoid possible effects of posttranslational modifications by alcohol or its metabolites. The lipid and protein concentrations of both intermediate density lipoprotein and low density lipoprotein were lower among the alcohol abusers than among the controls, those with E4 having the highest low density lipoprotein masses in both groups. In the alcohol abusers with E4 only the high density lipoprotein (HDL)-2 lipid and protein concentrations were higher than in the controls with respective phenotype group, whereas both HDL2 and HDL3 were higher in alcohol abusers with other apo E phenotypes, suggesting that apo E modulates the alcohol-effect on HDL subfractions. This effect was not explained by cholesteryl ester transfer protein activity, which was lower in the alcohol abusers (25 to 34%, p
Drinking alcohol has multiple effects on lipoprotein metabolism that lead to alterations, such as low levels of LDL and lipoprotein (a) and high levels of HDL. The protective effects of alcohol against coronary heart disease may be partly mediated by these lipoprotein changes. This review will focus mainly on the mechanisms potentially responsible for the alcohol-induced alterations in lipoprotein metabolism. Some common pitfalls in alcohol studies will also be discussed.
Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters from HDL to apoB-containing lipoproteins. Since alcoholics have high HDL cholesterol and low LDL cholesterol levels, a defect in cholesteryl ester transfer could be responsible for the alcohol-induced alteration in cholesterol distribution between lipoproteins. To test this hypothesis, we compared CETP activity in plasma from 30 alcoholics without severe liver damage and 16 control subjects. Plasma CETP activity was 28% lower in the alcoholics compared with the controls (P less than 0.001), while the teetotallers among the latter had slightly higher CETP activity than those who consumed alcohol in moderation. CETP activity increased slowly after ethanol withdrawal, but did not reach the control level within the 7-day observation period. A positive correlation was observed between plasma CETP activity and the LDL cholesterol HDL cholesterol ratio (r = 0.480, P less than 0.002), whereas CETP activity showed a negative correlation with HDL cholesterol level (r = -0.467, P less than 0.001). The results indicate that defective transfer of cholesteryl esters from HDL to LDL contributes to the high HDL cholesterol levels in alcoholics.
The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol:triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospholipid:cholesterol ratios were increased by 36% and 46%, respectively. IDL mass and protein concentrations, and particularly the fractional cholesteryl ester content of IDL tended to be low in the alcoholics. The plasma concentrations of all the LDL components except triglycerides were reduced in the alcoholics, resulting in a lower LDL cholesterol:triglyceride ratio. During the four day abstinence, when the lipoprotein values were followed in 15 alcoholic subjects, the abnormalities in VLDL composition and LDL plasma concentrations changed towards the values of the controls. In six alcoholic subjects who volunteered for LDL kinetic studies the fractional catabolic rate for LDL particles isolated immediately after the drinking period and seven days later were the same. These studies suggest that the alterations in all the apoB containing lipoproteins may contribute to the delayed progression of atherosclerosis observed in alcohol users.
Plasma cholesteryl esters, synthesized within high density lipoproteins (HDL), may be transferred from HDL particles to other lipoproteins by plasma cholesteryl ester transfer protein (CETP). Alcohol consumption is associated with increased HDL cholesterol concentration and reduced plasma CETP activity. The alcohol-induced decrease in CETP activity may be due to a low concentration of CETP in plasma or the inhibition of CETP by specific inhibitor proteins or alterations in the composition of plasma lipoproteins. The first two possibilities are studied further in this paper using data on 47 alcohol abusers and 31 control subjects. The activity of CETP was measured as the rate of cholesteryl ester transfer between radio-labeled low density lipoproteins and unlabeled HDL using an in vitro method independent of endogenous plasma lipoproteins. Plasma CETP concentration was determined by a Triton-based radioimmunoassay. The alcohol abusers consuming alcohol (on average 154 g/day) had 28% higher HDL cholesterol (P less than 0.01), 27% lower plasma CETP concentration (P less than 0.001), and 22% lower plasma CETP activity (P less than 0.001) than the controls. Plasma CETP concentration showed a negative correlation with HDL cholesterol among all the subjects (r = -0.317, P less than 0.01) but not among the alcohol abusers alone (r = -0.102, N. S.). During 2 weeks of alcohol withdrawal, plasma CETP concentration and activity of 8 subjects increased, whereas HDL cholesterol decreased by 42% (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)