Antiretrovirals induce endothelial dysfunction via an oxidant-dependent pathway and promote neointimal hyperplasia.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Bo JiangTammy R Dugas

Abstract

Human immunodeficiency virus-1 antiretroviral treatment is associated with an increased incidence of atherosclerosis. We hypothesized that antiretrovirals directly impair endothelial function after short-term exposure and that with chronic exposure, this dysfunction promotes a proliferative response, inducing neointimal hyperplasia, thus contributing to vascular lesion formation. To test this hypothesis, we treated mice with the nucleoside reverse transcriptase inhibitor azidothymidine (AZT), the protease inhibitor indinavir, or AZT + indinavir. Treatment with AZT or AZT + indinavir for 5 days impaired endothelium-dependent vessel relaxation. Though indinavir treatment alone did not alter vessel relaxation, it potentiated the impairment of endothelium-dependent relaxation induced by AZT. Coadministration of the antioxidant Mn (III) tetrakis (1-methyl-4-pyridyl) porphyrin attenuated antiretroviral-induced endothelial dysfunction, suggesting that oxidant production may have a causal role in the observed endothelial dysfunction. To test whether the antiretrovirals promote a proliferative response following endothelial dysfunction, we treated mice with antiretrovirals for 14 days and then induced a carotid endothelial injury. Two w...Continue Reading

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Citations

May 4, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Stephen Y XueTammy R Dugas
May 9, 2012·Free Radical Biology & Medicine·Kristi M Porter, Roy L Sutliff
Jun 9, 2015·Journal of Biomechanics·Alexander W CaulkRudolph L Gleason
Jan 18, 2018·Current Opinion in Nephrology and Hypertension·Jean Hou, Cynthia C Nast
Jun 19, 2018·AIDS·Virawudh SoontornniyomkijScott L Letendre
Sep 24, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yi-Fan ChenTammy R Dugas
Jul 3, 2021·Medicina·Mircea BajdechiSorin Rugina

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