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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1694.)
© 2007 American Heart Association, Inc.

Brief Reviews

Peripheral Circadian Clocks in the Vasculature

Dermot F. Reilly; Elizabeth J. Westgate; Garret A. FitzGerald

From the Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia.

Correspondence to Garret A FitzGerald, Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104. E-mail garret{at}spirit.gcrc.upenn.edu

Living organisms have adapted to the daily rotation of the earth and regular changes in the light environment. Life forms anticipate environmental transitions, adapt their own physiology, and perform activities at behaviorally advantageous times during the day. This is achieved by means of endogenous circadian clocks that can be synchronized to the daily changes in external cues, most notably light and temperature. For many years it was thought that neurons of the suprachiasmatic nucleus (SCN) uniquely controlled circadian rhythmicity of peripheral tissues via neural and humoral signals. The cloning and characterization of mammalian clock genes revealed that they are expressed in a circadian manner throughout the body. It is now accepted that peripheral cells, including those of the cardiovascular system, contain a circadian clock similar to that in the SCN. Many aspects of cardiovascular physiology are subject to diurnal variation, and serious adverse cardiovascular events including myocardial infarction, sudden cardiac death, and stroke occur with a frequency conditioned by time of day. This has raised the possibility that biological responses under the control of the molecular clock might interact with environmental cues to influence the phenotype of human cardiovascular disease.

Endogenous circadian clocks are present in the cardiovascular system. At the molecular level output from these oscillators manifests as circadian expression of transcripts for many genes relevant to cardiovascular disease. In this review we discuss the potential contribution of these molecular oscillators to the observed diurnal variation in cardiovascular disease.

Key Words: circadian • clock • diurnal • peripheral • SCN

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