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(Circulation. 2009;119:1510-1517.)
© 2009 American Heart Association, Inc.

Vascular Medicine

Vascular Disease in Mice With a Dysfunctional Circadian Clock

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

From the Department of Pharmacology and Toxicology (C.B.A., M.Z., G.B.S., D.J.F., R.D.R.), Department of Physiology (D.W.S.), Vascular Biology Center (D.W.S., D.J.F.), and Cardiology Division, Department of Medicine (G.R.), Medical College of Georgia, Augusta.

Correspondence to R. Daniel Rudic, PhD, Department of Pharmacology and Toxicology, Medical College of Georgia, 1120 15th St, CB-3621, Augusta, GA 30912. E-mail rrudic{at}mcg.edu

Received October 10, 2008; accepted December 30, 2008.

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.

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CLINICAL PERSPECTIVE

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Clinical Summaries
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