Alcoholism and atherosclerosis have been and continue to be major health problems in the U.S. and many other western nations in terms of their high mortality, their high direct and indirect economic impacts on society and in terms of their abilities to cause human suffering. Despite the high prevalence of these maladies, the effects of alcohol (ethanol consumption on the pathogenesis of atherosclerosis is still somewhat controversial. There are both anecdotal and experimental clinical studies suggesting that a moderate consumption of alcohol reduces the risk of coronary artery disease (CAD), the most important expression of atherosclerosis. Other studies have shown that heavy drinking increases the risk of CAD and the mortality associated with it. The news media, much to the delight of the liquor and wine industry, has promulgated the idea that moderate consumption of alcohol (i.e. a glass or two of wine or shot or two of hard liquor per day) reduces the risk of CAD. In view of the fact that there is still some uncertainty about this assertion, and in the view of the many potential detrimental effects of alcohol, it is important to further investigate this problem. One approach to this question is to explore the role of alcohol in the pathogenesis of atherosclerosis in greater depth using a good animal model. The hyperlipidemic C57BL/6 female mouse model for atherosclerosis developed by Paigan et al is an excellent model for atherosclerosis and C57BL/6 mice have also been used extensively in alcohol studies, including its effects on-the immune response. Our short term aims are to: 1. Establish the model in C57BL/6 mice by combining the atherogenic model with the alcohol model; 2. Determine the effect of three doses (high, medium and low) of alcohol on the development and progression of atherosclerotic lesions; and 3. Begin to examine the mechanism of alcohol effects on atherogenesis by analyzing the serum lipoproteins (especially HDL and Apoprotein Al) And immunologic alterations in ethanol-atherogenic diet treated mice. The atherogenic model has been well-established in our laboratory. We will attempt to combine this model with the Lieber-DeCarli liquid ethanol diet to create an all liquid diet that will combine the effectiveness and utility of both diets and yet not be lethal or debilitating to the mice. The use of three doses of ethanol consumption is an attempt to simulate some of the possible levels of consumption and blood ethanol levels in humans. Our long term goals are to explore in greater depth the molecular mechanisms of the immunologic and lipid alterations mediating the effects of ethanol on the pathogenesis of atherosclerosis.
| Emeson, E E; Manaves, V; Emeson, B S et al. (2000) Alcohol inhibits the progression as well as the initiation of atherosclerotic lesions in C57Bl/6 hyperlipidemic mice. Alcohol Clin Exp Res 24:1456-66 |
| Emeson, E E; Shen, M L; Bell, C G et al. (1996) Inhibition of atherosclerosis in CD4 T-cell-ablated and nude (nu/nu) C57BL/6 hyperlipidemic mice. Am J Pathol 149:675-85 |
| Emeson, E E; Manaves, V; Singer, T et al. (1995) Chronic alcohol feeding inhibits atherogenesis in C57BL/6 hyperlipidemic mice. Am J Pathol 147:1749-58 |
