HAART drugs induce mitochondrial damage and intercellular gaps and gp120 causes apoptosis

Milan Fiala*, Thomas Murphy, James MacDougall, Wendy Yang, Alfonso Luque, Luisa Iruela-Arispe, John Cashman, Georgette Buga, Russel E. Byrns, Giuseppe Barbaro, James Arthos

*Corresponding author for this work

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

HIV-1 infection is associated with serious cardiovascular complications, but the roles of HIV-1, viral proteins, and highly active antiretroviral therapy (HAART) drugs are not understood. HAART decreases the overall risk of heart disease but leads to metabolic disturbances and possibly coronary artery disease. We investigated toxicities of HIV-1, HIV-1 glycoprotein 120(gp120), and HAART drugs for human coronary artery endothelial cells (CAECs), brain microvascular endothelial cells, and neonatal rat ventricular myocytes (NRVMs). HIV-1 and gp120, but not azidothymidine (AZT), induced apoptosis of NRVMs and CAECs. Ethylisothiourea, an inhibitor of nitric oxide synthase, inhibited apoptosis induction by gp120. AZT, HIV-1, and gp120 all damaged mitochondria of cardiomyocytes. HAART drugs, AZT, and indinavir, but not HIV-1, produced intercellular gaps between confluent endothelial cells and decreased transendothelial electrical resistance. In conclusion, HIV-1 and gp120 induce toxicity through induction of cardiomyocyte and endothelial cell apoptosis. HAART drugs disrupt endothelial cell junctions and mitochondria and could cause vascular damage.

Original languageEnglish (US)
Pages (from-to)327-337
Number of pages11
JournalCardiovascular Toxicology
Volume4
Issue number4
DOIs
StatePublished - Dec 7 2004

Keywords

  • Azidothymidine
  • Cardiomyocyte apoptosis
  • Coronary artery
  • Endothelial cells
  • Gp120
  • HAART toxicities
  • Indinavir
  • Interendothelial junctions
  • Mitochondria
  • Nitric oxide

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'HAART drugs induce mitochondrial damage and intercellular gaps and gp120 causes apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Fiala, M., Murphy, T., MacDougall, J., Yang, W., Luque, A., Iruela-Arispe, L., Cashman, J., Buga, G., Byrns, R. E., Barbaro, G., & Arthos, J. (2004). HAART drugs induce mitochondrial damage and intercellular gaps and gp120 causes apoptosis. Cardiovascular Toxicology, 4(4), 327-337. https://doi.org/10.1385/CT:4:4:327