Cardiovascular Toxicology

, Volume 19, Issue 6, pp 500–509 | Cite as

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. DugasEmail author


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.


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



Funding for these studies was provided by discretionary sources within the Department of Comparative Biomedical Sciences (LSU School of Veterinary Medicine).

Compliance with Ethical Standards

Conflicts of interest

The authors have no conflicts of interest related to this study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yi-Fan Chen
    • 1
  • Valeria Y. Hebert
    • 2
  • Krisztian Stadler
    • 3
  • Stephen Y. Xue
    • 2
  • Kate Slaybaugh
    • 2
  • Elliot Luttrell-Williams
    • 2
  • Mitzi C. Glover
    • 4
  • David M. Krzywanski
    • 5
  • Tammy R. Dugas
    • 1
    Email author
  1. 1.Comparative Biomedical SciencesLSU School of Veterinary MedicineBaton RougeUSA
  2. 2.Pharmacology, Toxicology and NeuroscienceLSU Health Sciences CenterShreveportUSA
  3. 3.Oxidative Stress and Disease LaboratoryPennington Biomedical Research CenterBaton RougeUSA
  4. 4.Clinical Laboratory Sciences, School of Allied Health ProfessionsLSU Health Sciences CenterNew OrleansUSA
  5. 5.Cellular Biology and AnatomyLSU Health Sciences CenterShreveportUSA

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