Vascular disease in mice with a dysfunctional circadian clock.

Abstract:

BACKGROUND: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, Bmal1-knockout and Clock mutant. In addition, naive aortas from Bmal1-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 Bmal1-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.

journal_name

Circulation

journal_title

Circulation

authors

Anea CB,Zhang M,Stepp DW,Simkins GB,Reed G,Fulton DJ,Rudic RD

doi

10.1161/CIRCULATIONAHA.108.827477

subject

Has Abstract

pub_date

2009-03-24 00:00:00

pages

1510-7

issue

11

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.108.827477

journal_volume

119

pub_type

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