Vascular disease in mice with a dysfunctional circadian clock

Ciprian B. Anea, Maoxiang Zhang, David W. Stepp, G. Bryan Simkins, Guy Reed, David J. Fulton, R. Daniel Rudic

Research output: Contribution to journalArticle

160 Scopus citations

Abstract

Cardiovascular disease is the leading cause of death for both men and women in the United States and the world. A profound pattern exists in the time of day at which the death occurs; it is in the morning, when the endothelium is most vulnerable and blood pressure surges, that stroke and heart attack most frequently happen. Although the molecular components of circadian rhythms rhythmically oscillate in blood vessels, evidence of a direct function for the "circadian clock" in the progression to vascular disease is lacking. Methods and Results-In the present study, we found increased pathological remodeling and vascular injury in mice with aberrant circadian rhythms, Bmall-knockout and Clock mutant. In addition, naive aortas from Bmall- knockout and Clock mutant mice exhibit endothelial dysfunction. Akt and subsequent nitric oxide signaling, a pathway critical to vascular function, was significantly attenuated in arteries from Bmall-knockout mice.Conclusions-Our data reveal a new role for the circadian clock during chronic vascular responses that may be of significance in the progression of vascular disease.

Original languageEnglish (US)
Pages (from-to)1510-1517
Number of pages8
JournalCirculation
Volume119
Issue number11
DOIs
StatePublished - Mar 24 2009

Keywords

  • Circadian rhythm
  • Endothelium
  • Remodeling
  • Thrombus
  • Vasculature

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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