Cardiomyopathy in a murine model of AIDS: Evidence of reactive nitrogen species and corroboration in human HIV/AIDS cardiac tissues

Alysia A. Chaves, Michael J. Mihm, Brandon L. Schanbacher, Anupam Basuray, Cynthia Liu, Leona W. Ayers, John Anthony Bauer

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)108-118
Number of pages11
JournalCardiovascular Research
Volume60
Issue number1
DOIs
StatePublished - Nov 1 2003

Bibliographical note

Funding Information:
This study was supported in part by grants from the National Institutes of Health (HL-63067 and HL-59791), and a grant from AHA Ohio–West Virginia Affiliate. Human specimens were provided by the NCI’s AIDS and Cancer Specimen Resource

Keywords

  • AIDS
  • Cardiomyopathy
  • HIV
  • Nitric oxide
  • Reactive nitrogen species
  • Retrovirus

ASJC Scopus subject areas

  • General Medicine

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