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HIV-1 induces cardiomyopathy by cardiomyocyte invasion and gp120, tat, and cytokine apoptotic signaling

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Abstract

We examined heart tissues of AIDS patients with or without HIV cardiomyopathy (HIVCM) by immunohistocheistry, in situ polymerase chain reaction, in situ riboprobe hybridization, and the TUNEL technique for apoptosis. In HIVCM tissues, only inflammatory cells, but not endothelial cells or cardiomyocytes, displayed HIV-1 DNA and RNA. However, macrophages, lymphocytes, and—in a patchy fashion—cardiomyocytes and endothelial cells exhibited virus envelope protein gp 120. Macrophages infiltrated the myocardium in a perivascular fashion and expressed tumor necrosis factor family ligands; adjacent cardiomyocytes suffered apopotosis. in vitro HIV-1 strongly invaded neonatal rat ventricular myocytes (NRVMs) and coronary artery endothelial cells (CAECs) and induced microvilli but did not replicate. HIV-1, gp120, or Tat induced Erk 1/2 phosphorylation, activation of caspase-3, and apoptosis of NRVMs and CAECs; all of these were inhibited by a MAPK/ERK-kinase (MEK) inhibitor U0126. The pathogenesis of HIVCM involves HIV-1 replication in inflammatory cells and induction of cardiomyocyte apoptosis by (1) the extrinsic pathway through apoptotic ligands and (2) the intrinsic pathway through direct virus entry and gp120-and Tat-proapoptotic signaling.

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Authors and Affiliations

  1. Department of Medicine, Greater Los Angeles VA Medical Center, UCLA CHS 63-090, 10833 Le Conte Avenue, 90095-1760, Los Angeles, CA

    Milan Fiala MD, Kenix Tran & Wendy Yang

  2. Cardlovascular Research Laboratory, The Johns Hopkins University School of Medicine, Baltimore, MD

    Milan Fiala MD & Kenneth P. Roos

  3. Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, MD

    Waldemar Polik & Timothy Alce

  4. Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, CA

    Jian-Hua Qiao

  5. Huntington Medical Research Institutes, Pasadena, CA

    Albert S. Lossinsky

  6. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

    James Arthos

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  1. Milan Fiala MD
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  2. Waldemar Polik
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  3. Jian-Hua Qiao
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  4. Albert S. Lossinsky
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Correspondence to Milan Fiala MD.

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Fiala, M., Polik, W., Qiao, JH. et al. HIV-1 induces cardiomyopathy by cardiomyocyte invasion and gp120, tat, and cytokine apoptotic signaling. Cardiovasc Toxicol 4, 97–107 (2004). https://doi.org/10.1385/CT:4:2:097

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  • DOI: https://doi.org/10.1385/CT:4:2:097

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