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Author Notes:

Correspondence: Email: rrudic@gru.edu

Ciprian B. Anea and Maoxiang Zhang contributed equally to this work.

Conceived and designed the experiments: CBA MZ RDR.

Performed the experiments: CBA MZ AMM YOK PP FC.

Analyzed the data: CBA MIA MZ.

Contributed reagents/materials/analysis tools: CMMH DWS DF RDR.

Wrote the manuscript: CBA RDR.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This work was supported in part by grants from the National Institutes of Health (HL089576).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • MULTIDISCIPLINARY SCIENCES
  • SMOOTH-MUSCLE-CELLS
  • OXIDATIVE STRESS
  • GENE-EXPRESSION
  • NAD(P)H OXIDASE
  • ANGIOTENSIN-II
  • NADPH OXIDASES
  • BLOOD-PRESSURE
  • MICE
  • DYSFUNCTION
  • SUPEROXIDE
  • Circadian rhythms
  • Circadian oscillators
  • Smooth muscle cells
  • Endothelial cells
  • Hydrogen peroxide
  • Gene expression
  • Genetic oscillators
  • Superoxides

Circadian Clock Control of Nox4 and Reactive Oxygen Species in the Vasculature

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Journal Title:

PLoS ONE

Volume:

Volume 8, Number 10

Publisher:

, Pages e78626-e78626

Type of Work:

Article | Final Publisher PDF

Abstract:

Recent studies have shown that circadian clock disruption is associated with pathological remodeling in the arterial structure and vascular stiffness. Moreover, chronic circadian disruption is associated with dysfunction in endothelial responses and signaling. Reactive oxygen species have emerged as key regulators in vascular pathology. Previously, we have demonstrated that circadian clock dysfunction exacerbates superoxide production through eNOS uncoupling. To date, the impact of circadian clock mutation on vascular NADPH oxidase expression and function is not known. The goal in the current study was to determine if the circadian clock controls vascular Nox4 expression and hydrogen peroxide formation in arteries, particularly in endothelial and vascular smooth muscle cells. In aorta, there was an increase in hydrogen peroxide and Nox4 expression in mice with a dysfunctional circadian rhythm (Bmal1-KO mice). In addition, the Nox4 gene promoter is activated by the core circadian transcription factors. Lastly, in synchronized cultured human endothelial cells, Nox4 gene expression exhibited rhythmic oscillations. These data reveal that the circadian clock plays an important role in the control of Nox4 and disruption of the clock leads to subsequent production of reaction oxygen species.

Copyright information:

© 2013 Anea et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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