Antigenic stimulation in the simian model of HIV infection yields dilated cardiomyopathy through effects of TNFα
- 12 March 2008
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in AIDS
- Vol. 22 (5), 585-594
- https://doi.org/10.1097/qad.0b013e3282f57f61
Abstract
OBJECTIVE: To investigate a role for endogenous myocardial cytokine production in the development of HIV-associated cardiomyopathy. DESIGN: Cardiomyopathy is a late-stage sequela of HIV infection. Although pathogenesis of this condition in HIV infection is poorly defined, inflammatory cytokines are recognized for their detrimental effects on myocardial structure and function. HIV infection is characterized by chronic immune activation and inflammatory cytokine dysregulation. As the myocardium itself is a rich potential source of inflammatory cytokines, HIV-mediated cytokine dysregulation may be an important contributor to development of HIV cardiomyopathy. An antigenic stimulation protocol conducted in the simian immunodeficiency virus (SIV) model of HIV infection was used to study the effects of endogenous cytokine production on myocardial structure and function. METHODS: Twenty-six rhesus monkeys were assigned to treatment groups for a 35-day study. Animals were SIV-infected; SIV-infected and treated with killed Mycobacterium avium complex bacteria (MAC); SIV-infected, MAC-treated, and given the TNFalpha antagonist etanercept; or uninfected and MAC-treated. All animals were subjected to weekly echocardiographic studies. Hearts were collected for further evaluation at euthanasia. RESULTS: SIV-infected, MAC-treated animals developed significant systolic dysfunction [left ventricular ejection fraction (LVEF) decline of 19 +/- 2%] and ventricular chamber dilatation [left ventricular end-diastolic diameter (LVEDD) increase of 26 +/- 6%] not seen in other groups. Concurrent treatment with etanercept prevented development of these changes, implicating a causative role of myocardial TNFalpha. CONCLUSIONS: SIV-infected animals develop exaggerated myocardial pathology on stimulation with the ubiquitous environmental agent MAC. These responses are TNFalpha-dependent and may play a significant role in the development of cardiomyopathy in HIV infectionKeywords
This publication has 31 references indexed in Scilit:
- Phenotypic Variation in Myocardial Macrophage Populations Suggests a Role for Macrophage Activation in SIV-Associated Cardiac DiseaseAIDS Research and Human Retroviruses, 2007
- SIV-Associated Myocarditis: Viral and Cellular Correlates of Inflammation SeverityAIDS Research and Human Retroviruses, 2006
- Autoinduction of tumor necrosis factor-α in FRTL-5 rat thyroid cellsJournal of Endocrinology, 2005
- Cytokine-Induced Modulation of Cardiac FunctionCirculation Research, 2004
- Immunopathogenesis of HIV-related heart muscle diseaseAIDS, 2003
- Mediators in HIV-associated cardiovascular diseaseAIDS, 2003
- Inflammatory Mediators and the Failing HeartCirculation Research, 2002
- HIV Type 1 Glycoprotein 120 Inhibits Cardiac Myocyte ContractionAIDS Research and Human Retroviruses, 2002
- Cardiac Disease in Transgenic Mice Expressing Human Immunodeficiency Virus-1 Nef in Cells of the Immune SystemThe American Journal of Pathology, 2002
- Host factors and the pathogenesis of HIV-induced diseaseNature, 1996