The results of a large number of epidemiologic studies indicate that long-term, regular consumption of alcoholic beverages at low to moderate levels (one to three drinks per day for months to years) decreases the incidence of coronary artery disease and improves survival in patients suffering myocardial infarctions. Some of the first evidence in favor of this concept was derived from studies examining the relationship between cardiovascular mortality rates and dietary fat consumption in several European and North American countries. Whereas there was direct correlation noted between these variables in most Westernized societies, France was a notable exception in that this population demonstrated a much lower risk of death from cardiovascular disease than would be predicted from the levels of fat in their diets. A potential explanation for this "French paradox" became apparent when red wine consumption was factored into the analysis. Although the antioxidant properties of red wine constituents were originally thought to largely explain its cardioprotective effects, subsequent epidemiologic evidence indicated that consumption of white wine, beer, or spirits was also beneficial. The latter observations pointed to the importance of ethanol per se in the beneficial actions of alcohol intake on cardiovascular mortality.
Subsequent studies directed at the mechanistic underpinnings for the cardioprotective effects of moderate ethanol consumption focused primarily on lipoprotein and hemostatic factors. However, ethanol intake maintains a significant association with reduced cardiovascular mortality even after controlling for its effects on plasma lipids, platelet function, and fibrinolytic activity. Very recent work indicates that antecedent ethanol ingestion induces the development of an anti-inflammatory phenotype in postcapillary venules such that these vessels fail to support leukocyte adhesion and emigration in postischemic tissues. Given the critical importance of infiltrating leukocytes in the pathogenesis of atherosclerosis and ischemia-reperfusion (I/R) injury, these new observations provide novel insight regarding the mechanisms whereby ethanol ingestion reduces the likelihood and extent of I/R injury in individuals at risk for cardiovascular disease. The purpose of this review is to summarize our current understanding of the mechanisms whereby ethanol consumption induces the adaptive transformation to a protected or defensive phenotype in postcapillary venules such that these vessels fail to support I/R-induced leukocyte adhesion and emigration. Understanding the signaling pathways that are invoked by ingestion of alcoholic beverages may provide a mechanistic rationale for the development of novel treatment interventions that target both the microcirculatory and parenchymal sequelae to I/R, but do not produce the negative social and pathophysiologic consequences of ethanol ingestion.
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