Cardiomyopathy in a murine model of AIDS: evidence of reactive nitrogen species and corroboration in human HIV/AIDS cardiac tissues.
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.
Chaves
Alysia A
AA
Center for Developmental Pharmacology and Toxicology, Columbus Children's Research Institute, Columbus, OH 43205, USA.
Mihm
Michael J
MJ
Schanbacher
Brandon L
BL
Basuray
Anupam
A
Liu
Cynthia
C
Ayers
Leona W
LW
Bauer
John Anthony
JA
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002311:Cardiomyopathy, Dilated / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D018450:Disease Progression; D004452:Echocardiography; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications*; D009206:Myocardium / Q000737:chemistry / Q000276:immunology; D012367:RNA, Viral / Q000032:analysis; D026361:Reactive Nitrogen Species / Q000032:analysis; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D012367:RNA, Viral; D026361:Reactive Nitrogen Species; D014443:Tyrosine; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C002744:3-nitrotyrosine