Alcohol feeding impedes early atherosclerosis in low-density lipoprotein receptor knockout mice: factors in addition to high-density lipoprotein-apolipoprotein A1 are involved.
The effect of alcohol feeding on the development of atherosclerosis was investigated in low-density lipoprotein receptor gene-knockout (LDLR-/-) mice. Eight-week-old male mice were pair-fed atherogenic liquid diets containing ethanol at different levels (w/v; group A, 5%; group B, 2.5%; and group C, 0%). Tissue sections of the heart were stained with Oil Red O to examine for fatty lesions in proximal aorta. Results showed that the lesion size of group A was 70% smaller than group C after 6 weeks. By contrast, the lesion size of group B was not significantly different from that of group C. Serum high-density lipoprotein-apolipoprotein A1 (apo A1) A1 in LDLR-/- mice was suppressed by feeding the atherogenic diet, but the decrease was negated by alcohol (both groups A and B). The effectiveness of 5% alcohol to protect against atherosclerosis waned with time, but was still noticeable at 12 weeks, even though serum apo A1 remained high. Serum apolipoprotein E was increased by the high fat diet, but not altered by alcohol in the diet. Our data, therefore, show that: (1) alcohol-feeding impedes early atherosclerosis in LDLR-/- mice (this effect of alcohol is dose-dependent); (2) the protective effect of alcohol is not entirely attributable to an elevated serum high-density lipoprotein-apo A1; and (3) severe impairment of lipoprotein metabolism due to a lack of low-density lipoprotein receptors can eventually overwhelm the protective effect of alcohol against atherosclerosis.
Dai
J
J
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Miller
B A
BA
Lin
R C
RC
D000428:Alcohol Drinking / Q000235:genetics / Q000473:pathology; D000437:Alcoholism / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D016632:Apolipoprotein A-I / Q000097:blood*; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology; D003324:Coronary Artery Disease / Q000235:genetics / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000473:pathology; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011973:Receptors, LDL / Q000235:genetics*
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D011973:Receptors, LDL