Cardiovascular Toxicology

, Volume 4, Issue 2, pp 97–107 | Cite as

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

  • Milan Fiala
  • Waldemar Polik
  • Jian-Hua Qiao
  • Albert S. Lossinsky
  • Timothy Alce
  • Kenix Tran
  • Wendy Yang
  • Kenneth P. Roos
  • James Arthos
Original Contributions

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.

Key Words

HIV cardiomyopathy cardiomyocyte apoptosis HIV-1 envelope protein gp120 HIV-1 protein Tat macrophage 

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Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Milan Fiala
    • 1
    • 2
  • Waldemar Polik
    • 3
  • Jian-Hua Qiao
    • 4
  • Albert S. Lossinsky
    • 5
  • Timothy Alce
    • 3
  • Kenix Tran
    • 1
  • Wendy Yang
    • 1
  • Kenneth P. Roos
    • 2
  • James Arthos
    • 6
  1. 1.Department of Medicine, Greater Los Angeles VA Medical CenterUCLA CHS 63-090Los Angeles
  2. 2.Cardlovascular Research LaboratoryThe Johns Hopkins University School of MedicineBaltimore
  3. 3.Oncology CenterThe Johns Hopkins University School of MedicineBaltimore
  4. 4.Department of PathologyDavid Geffen School of Medicine at UCLALos Angeles
  5. 5.Huntington Medical Research InstitutesPasadena
  6. 6.Laboratory of Immunoregulation, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesda

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