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.