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From Washington University School of Medicine, Department of Internal Medicine, Division of Atherosclerosis, Nutrition, and Lipid Research (A.S., R.A.K.S., M.A.L., G.S.), and Purina Mills Inc, St Louis, Mo; and Parke-Davis Pharmaceutical Research, Ann Arbor, Mich (M.P., T.R., D.H.).
Correspondence to Gustav Schonfeld, Washington University School of Medicine, Department of Internal Medicine, Division of Atherosclerosis, Nutrition, and Lipid Research, Campus Box 8046, 660 S Euclid Ave, St Louis, MO 63110-1093.
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 7
-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% alcoholtreated groups. Also, significant correlations were found between plasma cholesterol levels and total lesion area or lesion cholesterol contents. In experiment 2, the 10% alcoholtreated 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.
Key Words: atherosclerosis rabbit alcohol cholesterol aorta
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