Vascular endothelial toxicity induced by HIV protease inhibitor: Evidence of oxidant-related dysfunction and apoptosis

Reshma S. Baliga, Cynthia Liu, Dale G. Hoyt, Alysia A. Chaves, John Anthony Bauer

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


HIV-protease inhibitor (HIV-PI) drugs are critical for highly active antiretroviral therapy (HAART) efficacy, but several recent reports have suggested that metabolic and/or cardiovascular toxicities are associated with these drugs. Given the importance of the HIV-PI drug class and the widespread and chronic use of these agents in an expanding patient population, further understanding of this potential drug toxicity is imperative. Here, we investigated a role for direct endothelial toxicity induced by saquinavir (SAQ), the first HIV-PI drug marketed in the United States and still an important component of HAART therapies. In initial studies using isolated vascular tissues, we observed selective impairment of endothelium-dependent vasodilation with no effect on contractile responses. Subsequent studies using human endothelial cells in culture at clinically relevant concentrations (5 and 10 μM 2-48 h) demonstrated concentration-dependent increases in cell death, mainly via apoptosis rather than necrosis (determined via Annexin-V positive membrane labeling). Live cell imaging also demonstrated increased intracellular oxidant production (as measured by DCF fluorescence), which could be abrogated by incubation with the antioxidant N-acetylcysteine (NAC). NAC also prevented SAQ-induced apoptotic cell death. These data demonstrate that SAQ has direct toxicological effects on endothelial cells, and that the toxicity apparently involves apoptotic pathway activation via reactive oxygen and/or nitrogen species.

Original languageEnglish
Pages (from-to)199-206
Number of pages8
JournalCardiovascular Toxicology
Issue number2
StatePublished - 2004


  • Antioxidants
  • Apoptosis
  • Endothelium
  • HIV protease inhibitors
  • Reactive oxygen species
  • Saquinavir

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Vascular endothelial toxicity induced by HIV protease inhibitor: Evidence of oxidant-related dysfunction and apoptosis'. Together they form a unique fingerprint.

Cite this