© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Cardiomyopathy in a murine model of AIDS: evidence of reactive nitrogen species and corroboration in human HIV/AIDS cardiac tissues
aCenter for Developmental Pharmacology and Toxicology, Columbus Children's Research Institute, Columbus, OH 43205, USA
bDivision of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
cDepartment of Pathology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
dDepartment of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
*Corresponding author. Tel.: +1-614-722-2835; fax: +1-614-722-2774. Email address: bauerj{at}pediatrics.ohio-state.edu
Objective: Cardiomyopathy and other vascular complications are now recognized as significant components of HIV/AIDS pathogenesis. Although the mechanisms involved in cardiomyopathy are poorly defined, a role for direct retroviral action and/or focal infiltration of activated immune cells have been postulated. Here we investigated mechanisms in retrovirus associated cardiomyopathy using a well-defined mouse model of acquired immunodeficiency. Methods: Mice were dosed with LPBM5 retrovirus; cardiac performance was assessed by echocardiography followed by tissue collection at 5 and 10 weeks post-infection. Results: Contractile deficits were observed at 5 and 10 weeks post-retrovirus infection and preceded the development of overt immunodeficiency. Selective and widespread cardiac infiltration of CD68+ cells, but not neutrophils, mast cells, or eosinophils was also observed at both 5 and 10 weeks. LPBM5 retrovirus was readily detectable in cardiac samples by RT-PCR. Time dependent increases in cardiac protein nitration (biomarker of reactive nitrogen species) were observed and were correlated to the extent of cardiac dysfunction whereas no changes in NOSII occurred at 5 and 10 weeks. We corroborated the mouse findings using cardiac tissues and clinical findings from human HIV/AIDS autopsies. Conclusions: These studies demonstrated that cardiac myocyte protein nitration in AIDS related cardiomyopathies, rather than focal immune cell lesions characterize retrovirus associated cardiomyopathies and differentiate them from non-retroviral cardiomyopathies.
KEYWORDS Nitric oxide; Reactive nitrogen species; HIV; AIDS; Cardiomyopathy; Retrovirus
Time for primary review 37 days.
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