Alcohol increases plasma levels of cholesterol diet-induced atherogenic lipoproteins and aortic atherosclerosis in rabbits.
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 alpha-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.
Shaish
A
A
Washington University School of Medicine, Department of Internal Medicine, St Louis, MO 63110-1093, USA.
Pape
M
M
Rea
T
T
Srivastava
R A
RA
Latour
M A
MA
Hopkins
D
D
Schonfeld
G
G
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D001189:Aryl Hydrocarbon Hydroxylases; D002791:Cholesterol, Dietary / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004036:Diet, Atherogenic; D000431:Ethanol; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006937:Hypercholesterolemia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011973:Receptors, LDL / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics; D014810:Vitamin E / Q000097:blood
D001053:Apolipoproteins; D002791:Cholesterol, Dietary; D005227:Fatty Acids; D012333:RNA, Messenger; D011973:Receptors, LDL; D014810:Vitamin E; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C029009:steroid hormone 7-alpha-hydroxylase