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

Cardiovascular Toxicology
Reshma S BaligaJohn A Bauer

Abstract

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 microM, 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 antioxid...Continue Reading

Citations

Apr 29, 2010·Current Atherosclerosis Reports·Abdul HakeemMehmet Cilingiroglu
Sep 30, 2009·Expert Opinion on Drug Metabolism & Toxicology·David James Hooker, Catherine Louise Cherry
Jan 31, 2012·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Mandar S JoshiJohn Anthony Bauer
Jan 10, 2009·International Journal of Cardiology·Jean-Jacques MonsuezDaniel Vittecoq
Oct 18, 2008·Molecular Aspects of Medicine·Alessandra FraternaleMauro Magnani
Jul 2, 2016·Neurotoxicity Research·Ankit ShahAnil Kumar
Jun 19, 2018·AIDS·Virawudh SoontornniyomkijScott L Letendre
Jun 21, 2008·Circulation·Michael P DubéUNKNOWN Working Group 3
Jul 1, 2006·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Bo JiangTammy R Dugas
Jun 1, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Reshma S BaligaJohn A Bauer
Nov 19, 2013·Pharmaceutical Patent Analyst·Mitesh PatelAshim K Mitra
Aug 27, 2013·Expert Review of Cardiovascular Therapy·Rami Alharethi
Jun 6, 2008·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Erik R Kline, Roy L Sutliff
Dec 1, 2011·Sexual Health·William Chan, Anthony M Dart

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis