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
Circulationjournal_title
Circulationauthors
Anea CB,Zhang M,Stepp DW,Simkins GB,Reed G,Fulton DJ,Rudic RDdoi
10.1161/CIRCULATIONAHA.108.827477subject
Has Abstractpub_date
2009-03-24 00:00:00pages
1510-7issue
11eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.108.827477journal_volume
119pub_type
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