Cardiomyopathy and left ventricular dysfunction are prevalent in people with AIDS or chronic alcohol use. However almost nothing is known of the combined effects of retroviral infection plus alcohol on heart disease. Our murine retrovirus infection mimics much of the cytokine dysregulation found during HIV infection, prompting inflammatory damage for cardiac toxicity. We found that alcohol consumption exacerbated many immune, oxidative, and nutritional defects due to murine retrovirus infection. We found that alcohol + retrovirus exposure was particularly toxic, increasing Th2 and reducing Th1 cytokines, dramatically lowering cardiac vitamin E, increasing oxidation of cardiac lipids and synergistically promoting severe heart damage due to Coxsackie B3 infection. Our overall hypothesis is that the combination of ethanol + retroviral infection induces immune dysfunction and oxidation for increased cardiovascular disease. These effects should promote growth and pathogenesis of cardiotrophic pathogens. This hypothesis will be investigated using Coxsackie B infection of mice during retrovirus and/or ethanol exposure. Left ventricular function will be quantitated in vivo with interventricular catheter to define the ventricular dysfunction and characterize the effects of alcohol. We will determine the contribution of the inflammatory response, induced by alcohol and/or retroviral exposure, to myocardial ischemic events and infarctions. We will assert the immune mechanisms involving PMNs in amplifying ischemic injury during cocaine plus retroviral exposure. We will assess leukocyte adhesion and localization, platelet-leukocyte interactions, and blocking these cells' function with drugs to understand their role in ischemia and heart pump dysfunction induced by cocaine and/or retrovirus exposure. We will assert the cardiotoxic effects of alcohol exposure prior to as well as post retrovirus infection. Our model studies will increase understanding of etiology of alcohol + retrovirus-induced immune dysfunction in cardiac pathology. We will limit the deleterious cardiac effects of retroviral infection and alcohol exposure with our proven methods that prevented much of the cytokine dysregulation and oxidative damage to the heart: T-cell receptor Vbeta 8.1, multiple antioxidant, and vitamin E supplementation. We hypothesize that our treatments will restrict cytokine dysregulation and thus cardiotoxicity in retrovirally-infected, alcohol-exposed mice. Such studies could provide the basis for their application to reduce heart disease in alcohol-abusing, HIV-infected patients.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-K (M2))
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Wang, Lan-Hsiang
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University of Arizona
Schools of Public Health
United States
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Watson, Ronald Ross; Zibadi, Sherma; Vazquez, Randy et al. (2005) Nutritional regulation of immunosenescence for heart health. J Nutr Biochem 16:85-7
Lopez, Maria C; Watson, Ronald R (2005) Alterations in mesenteric lymph node T cell phenotype and cytokine secretion are associated with changes in thymocyte phenotype after LP-BM5 retrovirus infection. Clin Dev Immunol 12:249-57
Yu, Qianli; Larson, Douglas F; Slayback, Denise et al. (2004) Characterization of high-salt and high-fat diets on cardiac and vascular function in mice. Cardiovasc Toxicol 4:37-46
Yang, Bo; Larson, Douglas F; Watson, Ronald R (2004) Modulation of iNOS activity in age-related cardiac dysfunction. Life Sci 75:655-67
Sepulveda, Ramon Tomas; Marchalonis, John Jacob; Watson, Ronald Ross (2003) T-cell receptor V beta 8.1 peptide reduces coxsackievirus-induced cardiopathology during murine acquired immunodeficiency syndrome. J Cardiovasc Pharmacol 41:489-97
Weekes, John; Watson, Ronald R; Dunn, Michael J (2003) Murine retrovirus infection and the effect of chronic alcohol consumption: proteomic analysis of cardiac protein expression. Alcohol Alcohol 38:103-8
Chen, Yinhong; Davis-Gorman, Grace; Watson, Ronald R et al. (2003) Platelet CD62p expression and microparticle in murine acquired immune deficiency syndrome and chronic ethanol consumption. Alcohol Alcohol 38:25-30
Yu, Qianli; Larson, Douglas F; Watson, Ronald R (2003) Heart disease, methamphetamine and AIDS. Life Sci 73:129-40
Chen, Yinhong; Mendoza, Sam; Davis-Gorman, Grace et al. (2003) Neutrophil activation by murine retroviral infection during chronic ethanol consumption. Alcohol Alcohol 38:109-14
Sepulveda, R T; Watson, R R (2003) Immune control of coxsackievirus-induced cardiopathology. Cell Mol Biol (Noisy-le-grand) 49:171-80

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