Several recent studies have shown that cardiovascular dysfunction may be an important complication of HIV infection, but the exact incidence of this problem, and the mechanism(s) by which it develops have not been defined. Evidence of increased reactive oxygen intermediates (R0I's) has been found in blood and tissues of HIV patients and animal models of retroviral infection; these conditions have been implicated in HIV viral activation, cytokine production, and immune system dysfunction. As a free radical and potent oxidant (particularly when combined with superoxide anion), NO has recently been implicated in AIDS-related neurotoxicity and dementia. It is therefore possible that important changes in NO production or destruction processes may play a role in retroviral immunopathogenesis, particularly in cardiovascular complications. The long term objectives are to determine the mechanism(s) of retrovirus related cardiovascular complications, define the role(s) of NO in these changes, and examine how can they be prevented or resolved. A relevant and well-documented mouse model of retroviral infection that has been shown to develop cardiac damage during infection will be studied. In vivo cardiac dysfunction will be related to cardiac oxidative damage during retroviral infection, and changes in balance between NO production and destruction pathways will be examined during immunopathogenesis and cardiac impairment. The investigators will also design and test rational strategies to intervene. In related investigations they will determine the relation of endogenous NO in expired air to cardiovascular and pulmonary complications in HIV infected patients. These studies will provide important new information regarding the mechanisms of cardiac dysfunction in retroviral infection, and provide important new insights and strategies for an emerging problem.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059791-02
Application #
2796819
Study Section
Special Emphasis Panel (ZHL1-CSR-K (S1))
Project Start
1997-09-30
Project End
2002-09-29
Budget Start
1998-09-30
Budget End
1999-09-29
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Pharmacy
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Joshi, Mandar S; Tong, Liyue; Cook, Angela C et al. (2012) Increased myocardial prevalence of C-reactive protein in human coronary heart disease: direct effects on microvessel density and endothelial cell survival. Cardiovasc Pathol 21:428-35
Mihm, Michael J; Amann, Deborah M; Schanbacher, Brandon L et al. (2007) Cardiac dysfunction in the R6/2 mouse model of Huntington's disease. Neurobiol Dis 25:297-308
Chaves, Alysia A; Baliga, Reshma S; Mihm, Michael J et al. (2006) Bacterial lipopolysaccharide enhances cardiac dysfunction but not retroviral replication in murine AIDS: roles of macrophage infiltration and toll-like receptor 4 expression. Am J Pathol 168:727-35
Joshi, Mandar S; Julian, Mark W; Huff, Jennifer E et al. (2006) Calcineurin regulates myocardial function during acute endotoxemia. Am J Respir Crit Care Med 173:999-1007
Baliga, Reshma S; Chaves, Alysia A; Jing, Liang et al. (2005) AIDS-related vasculopathy: evidence for oxidative and inflammatory pathways in murine and human AIDS. Am J Physiol Heart Circ Physiol 289:H1373-80
Piao, Shengfu; Yu, Fushun; Mihm, Michael J et al. (2003) A simplified method for identification of human cardiac myosin heavy-chain isoforms. Biotechnol Appl Biochem 37:27-30
Chaves, Alysia A; Dech, Spencer J; Nakayama, Tomohiro et al. (2003) Age and anesthetic effects on murine electrocardiography. Life Sci 72:2401-12
Chaves, Alysia A; Mihm, Michael J; Schanbacher, Brandon L et al. (2003) Cardiomyopathy in a murine model of AIDS: evidence of reactive nitrogen species and corroboration in human HIV/AIDS cardiac tissues. Cardiovasc Res 60:108-18
Mihm, Michael J; Wattanapitayakul, Suvara K; Piao, Sheng-Fu et al. (2003) Effects of angiotensin II on vascular endothelial cells: formation of receptor-mediated reactive nitrogen species. Biochem Pharmacol 65:1189-97

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