Opposite effects of moderate and excess alcohol consumption on the atheroprotective process of the reverse cholesterol transport in vivo

Epidemiological studies worldwide revealed that light to moderate alcohol consumption is inversely correlated with cardiovascular morbidity and mortality, whereas consumption above recommended limits causes the loss and even the reversal of this beneficial activity. Cardiovascular disease (CVD) and atherosclerosis can be prevented or retarded by the process of reverse cholesterol transport (RCT), in which high density lipoproteins (HDL) drive the removal of excess cholesterol from the macrophages of the artery wall. Recent studies in vivo and in humans established the inverse relationship between RCT efficiency and atherosclerotic CVD. Moreover it has been proposed that the assessement of HDL function, evaluated as the ability to promote cell cholesterol efflux, the first step of RCT, may represent a valuable predictor of atherosclerosis extent. The aim of the present study was to evaluate whether a differential modulation of RCT may account for the dual effect of moderate and heavy consumption of alcohol on CVD. For this purpose, RCT was measured with a standardized, radioisotope-based technique in 3 groups of apolipoprotein E knock out mice: group I (n=10), receiving placebo, mimicking the abstainers; group II (n=10), receiving 0.8g/kg alcohol/day for 28 days, mimicking a moderate intake of ethanol; group III (n=10), receiving 0.8g/kg alcohol/day for 26 days, followed by the administration of 2.8g/kg alcohol/day for 2 days, mimicking a heavy intake. At the end of the treatment period, mice were sacrificed and radioactivity quantified in plasma, liver and feces. Alcohol intake caused a dose-dependent increase in plasma total cholesterol (272mg/dl+59, 283mg/dl+53, 374mg/dl+86 in group I, II and III respectively) and HDL-cholesterol (124mg/dl+27, 154mg/dl+37, 179mg/dl+38 in group I, II and III respectively). Interestingly, excess alcohol consumption significantly increased plasma LDL cholesterol (126mg/dl+40, 113mg/dl+25, 165mg/dl+65; in group I, II and III respectively) and triglycerides (110mg/dl+36, 88mg/dl+16, 136mg/dl+30; in group I, II and III respectively). The overall removal of radioactivity from macrophages along the RCT pathway was slightly higher in animals treated with moderate dose of alcohol: 12.2%+3.1, 15.1%+ 3.7; 13.3%+2.4; in group I, II and III respectively. In conclusion, moderate alcohol consumption is likely to promote the mobilization of radioactive cholesterol from macrophages, along the RCT pathway, thus suggesting the amelioration of this process. Differently, excess alcohol consumption seems not to significantly impair the process, but exerts deleterious effects on plasma lipoprotein profile. Further investigations, including the evaluation of HDL functionality, evaluated as the capacity to promote cell cholesterol efflux from cultured macrophages, could provide the mechanicistic explanation of these in vivo data.