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

Ciprian B. Anea, Maoxiang Zhang, Feng Chen, M. Irfan Ali, C. Michael M. Hart, David W. Stepp, Yevgeniy O. Kovalenkov, Ana Maria Merloiu, Paramita Pati, David Fulton, R. Daniel Rudic

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere78626
JournalPloS one
Volume8
Issue number10
DOIs
StatePublished - Oct 25 2013

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Circadian Clocks
circadian rhythm
Clocks
reactive oxygen species
Reactive Oxygen Species
blood vessels
Blood Vessels
Vascular Stiffness
Hydrogen Peroxide
hydrogen peroxide
NADPH Oxidase
Circadian Rhythm
Vascular Smooth Muscle
Superoxides
Endothelial cells
mice
Smooth Muscle Myocytes
Pathology
Aorta
aorta

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Circadian Clock Control of Nox4 and Reactive Oxygen Species in the Vasculature. / Anea, Ciprian B.; Zhang, Maoxiang; Chen, Feng; Ali, M. Irfan; Hart, C. Michael M.; Stepp, David W.; Kovalenkov, Yevgeniy O.; Merloiu, Ana Maria; Pati, Paramita; Fulton, David; Rudic, R. Daniel.

In: PloS one, Vol. 8, No. 10, e78626, 25.10.2013.

Research output: Contribution to journalArticle

Anea, CB, Zhang, M, Chen, F, Ali, MI, Hart, CMM, Stepp, DW, Kovalenkov, YO, Merloiu, AM, Pati, P, Fulton, D & Rudic, RD 2013, 'Circadian Clock Control of Nox4 and Reactive Oxygen Species in the Vasculature', PloS one, vol. 8, no. 10, e78626. https://doi.org/10.1371/journal.pone.0078626
Anea, Ciprian B. ; Zhang, Maoxiang ; Chen, Feng ; Ali, M. Irfan ; Hart, C. Michael M. ; Stepp, David W. ; Kovalenkov, Yevgeniy O. ; Merloiu, Ana Maria ; Pati, Paramita ; Fulton, David ; Rudic, R. Daniel. / Circadian Clock Control of Nox4 and Reactive Oxygen Species in the Vasculature. In: PloS one. 2013 ; Vol. 8, No. 10.
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