ETHANOL AND ATHEROSCLEROSIS

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The aim of the research is to adapt atherogenic diets that contain ethanol to studies of rabbit atherosclerosis. Atherosclerotic cardiovascular disease continues to be the leading cause of death and morbidity in Western societies. Ethanol taken in moderate amounts may have beneficial effects, while large amounts may be deleterious to the vascular system. However, very few studies have been performed of any direct effects of ethanol on atherosclerotic plaque formation. The paucity of studies probably reflects, at least in part, the difficulty of feeding rabbits ethanol in accurately quantifiable and sufficient amounts to test rigorously any hypotheses regarding ethanol and atherosclerosis in the absence of confounding effects of such as malnutrition and weight loss. We wish to test the hypothesis that ethanol ingestion directly affects the sizes and compositions of aortic atherosclerotic plaques. The cholesterol-fed New Zealand White (NZW) rabbit and the Watanabe Heritable Hyperlipidemic (WHHL) rabbit, two frequently used models of experimental atherosclerosis will be used. We provide preliminary evidence that a palatable liquid ethanol-containing diet has been devised. We propose to render this diet atherogenic by adding cholesterol. After feeding this diet with and without ethanol, we shall examine the effects of dietary ethanol on the sizes and cholesterol contents of aortic atherosclerotic lesions and plasma lipoproteins. Based on these results the cellular composition and the expression of certain genes critical in plaque development, and the regulation of lipoproteins may be examined in subsequent experiments. WHHL fed the regular liquid diet, with and without ethanol will be examined the same way. The necessary techniques and reagents are available in our laboratory and we have experience with rabbit atherosclerosis. The project is important because a nutritional plan for rabbits that routinely produces atherosclerosis in the absence of ethanol and one that also can deliver sufficient and quantifiable amounts of ethanol to mimic human ethanol intakes could open up new areas of investigation to those interested in studies of alcohol and atherogenesis. Demonstration of ethanol effects on lesion size and cholesterol content would help in the understanding of epidemiologic findings and lead to further experiments that may define new preventive and therapeutic approaches for atherosclerosis. The proposed work qualifies for funding under "more experienced investigators for testing new methods or techniques."