HIV-1 induces cardiomyopathyby cardiomyocyte invasion and gp120, Tat, and cytokine apoptotic signaling

TitleHIV-1 induces cardiomyopathyby cardiomyocyte invasion and gp120, Tat, and cytokine apoptotic signaling
Publication TypeJournal Article
Year of Publication2004
AuthorsFiala, M, Popik, W, Qiao, JH, Lossinsky, AS, Alce, T, Tran, K, Yang, W, Roos, KP, Arthos, J
JournalCardiovascular Toxicology
Volume4
Issue2
Pagination97-107
Date Published2004
KeywordsAnimals, Cardiac, Cardiomyopathies, Caspases, Cells, Cultured, Cytokines, DNA, Endothelial Cells, External, Gene Products, In Situ Hybridization, In Situ Nick-End Labeling, Myocytes, Newborn, RNA, Signal Transduction, tat, tat Gene Products, Viral
Abstract

We examined heart tissues of AIDS patients with or without HIV cardiomyopathy (HIVCM) by immunohistochemistry, 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 gp120. Macrophages infiltrated the myocardium in a perivascular fashion and expressed tumor necrosis factor family ligands; adjacent cardiomyocytes suffered apoptosis. 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.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/15371627