Coenzyme Q10 Alleviates Chronic Nucleoside Reverse Transcriptase Inhibitor-Induced Premature Endothelial Senescence

Yi Fan Chen, Valeria Y. Hebert, Krisztian Stadler, Stephen Y. Xue, Kate Slaybaugh, Elliot Luttrell-Williams, Mitzi C. Glover, David M. Krzywanski, Tammy R. Dugas

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Human immunodeficiency virus (HIV)-infected patients undergoing antiretroviral therapy are afforded an increased lifespan but also exhibit an elevated incidence of cardiovascular disease. HIV therapy uses a combination drug approach, and nucleoside reverse transcriptase inhibitors (NRTI) are a backbone of this therapy. Endothelial dysfunction is an initiating event in cardiovascular disease etiology, and in our prior studies, NRTIs induced an endothelial dysfunction that was dependent upon mitochondrial oxidative stress. Moreover, short-term NRTI administration induced a mitophagy-associated endothelial toxicity and increased reactive oxygen species (ROS) production that was rescued by coenzyme Q10 (Q10) or overexpression of a mitochondrial antioxidant enzyme. Thus, our objective was to examine mitochondrial toxicity in endothelial cells after chronic NRTI treatment and evaluate Q10 as a potential adjunct therapy for preventing NRTI-induced mitochondrial toxicity. Human aortic endothelial cells (HAEC) were exposed to chronic NRTI treatment, with or without Q10. ROS production, cell proliferation rate, levels of senescence, and mitochondrial bioenergetic function were determined. Chronic NRTI increased ROS production but decreased population doubling. In addition, NRTI increased the accumulation of β-galactosidase, indicative of an accelerated rate of senescence. Moreover, ATP-linked respiration was diminished. Co-treatment with Q10 delayed the onset of NRTI-induced senescence, decreased ROS production and rescued the cells’ mitochondrial respiration rate. Thus, our findings may suggest antioxidant enrichment approaches for reducing the cardiovascular side effects of NRTI therapy.

Original languageEnglish (US)
Pages (from-to)500-509
Number of pages10
JournalCardiovascular Toxicology
Volume19
Issue number6
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

Keywords

  • Coenzyme Q10
  • Endothelial cells
  • Human immunodeficiency virus (HIV)
  • Mitochondria
  • Nucleoside reverse transcriptase inhibitors (NRTI)
  • Senescence

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine

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