Alcohol Increases Plasma Levels of Cholesterol Diet–Induced Atherogenic Lipoproteins and Aortic Atherosclerosis in Rabbits

Abstract

Abstract The purpose of the present study was to reexamine the relationship between alcohol and atherosclerosis. Two experiments were performed: The first contained three groups of New Zealand White (NZW) female rabbits. The control group was fed a cholesterol-containing liquid diet and the other two groups were fed the same diet with either 20% or 30% of the calories supplied by alcohol. The second experiment had two treatments: one control group and another group fed a 10% alcohol diet. In experiment 1, alcohol at the 20% and 30% levels increased VLDL and LDL but not HDL compared with levels in control rabbits. Hepatic mRNA levels of apolipoprotein (apo) A-I, apoB, and 7α-hydroxylase were not affected by alcohol. However, the LDL-receptor mRNA was decreased to half of control values by either 20% or 30% alcohol. Lesion areas and aortic cholesterols were significantly increased in the 20% and 30% alcohol–treated groups. Also, significant correlations were found between plasma cholesterol levels and total lesion area or lesion cholesterol contents. In experiment 2, the 10% alcohol–treated rabbits showed no differences in circulating lipoproteins, LDL-receptor mRNA, or lesion formation above that observed in controls. These experiments suggest that alcohol substituted at 20% or 30% of the dietary calories induces hypercholesterolemia and more aortic atherosclerotic lesions. The alcohol-induced accumulation of VLDL and LDL was accompanied by low hepatic LDL-receptor mRNA levels, suggesting that alcohol may affect LDL-receptor expression and rates of lipoprotein clearance, but more experiments are needed to evaluate this possibility.