Chronic Alcohol Exposure Modulates Atherosclerotic Plaque Vulnerability in ApoE Knockout Mice

ABSTRACT Aim: This study aimed to examine the effect of chronic alcohol consumption on the development and progression of atherosclerosis in apolipoprotein E‐knockout (ApoE −/− ) mice. Method: Male ApoE −/− mice, aged 8 weeks, were randomly assigned to four groups: control, model, low‐dose alcohol, and high‐dose alcohol. The mice were fed a normal chow or high‐fat diet for 14 weeks, with water provided alongside 1% (v/v) or 5% (v/v) alcohol solutions. Results: Mice in the 1% (v/v) alcohol group showed a significant increase in subcutaneous and epididymal fat compared to those in the model group. However, basal metabolic markers remained unchanged in the 5% (v/v) alcohol group, although water intake was significantly lower. Histological analyses of the experimental groups exposed to alcohol revealed no protective effects against atherosclerosis in the aortic tree or plaque deposition in the aortic root. Additionally, no significant changes were observed in the macrophages and smooth muscle cells within the aortic root plaques. Nevertheless, low‐dose alcohol exposure protected plaque vulnerability compared with the model group, whereas high‐dose alcohol had no effect. Transcriptomic analysis of aortic tissue further indicated that alcohol consumption reduced the expression of genes related to lipid transport and metabolic abnormalities.