Vascular disease in mice with a dysfunctional circadian clock.
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.


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.
Anea
Ciprian B
CB
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA.
Zhang
Maoxiang
M
Stepp
David W
DW
Simkins
G Bryan
GB
Reed
Guy
G
Fulton
David J
DJ
Rudic
R Daniel
RD
D056930:ARNTL Transcription Factors; D000818:Animals; D001011:Aorta / Q000502:physiology; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D056926:CLOCK Proteins; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D002340:Carotid Artery Diseases / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D021081:Chronobiology Disorders / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005263:Femoral Artery / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013927:Thrombosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D015534:Trans-Activators / Q000235:genetics*
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D015534:Trans-Activators; C538961:Bmal1 protein, mouse; C496315:Nos3 protein, mouse; C538944:Clock protein, mouse