Title: THE CIRCADIAN CLOCK WITHIN THE HEART: POTENTIAL INFLUENCE ON MYOCARDIAL GENE EXPRESSION, METABOLISM, AND FUNCTION Author
Submitted to: American Journal of Physiology - Heart and Circulatory Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 1, 2005
Publication Date: January 1, 2006
Citation: Young, M.E. 2006. The circadian clock within the heart: potential influence on myocardial gene expression, metabolism, and function. American Journal of Physiology - Heart and Circulatory Physiology. 290(1):H1-H16. Interpretive Summary: It is known that heart function changes over the course of the day. It is also known that more people die from heart disease in the early hours of the morning. We have shown previously that the heart possesses a mechanism that allows this organ to perceive the time of day. This mechanism, known as the circadian clock, allows the heart to prepare for routine changes that occur during the daily life of an organism (for example, sleeping during the night, and waking in the morning). This article discusses what is known about the function of the circadian clock in the heart, an whether loss of the clock contributes to heart disease.
Technical Abstract: It is becoming increasingly clear that the intrinsic properties of both the heart and vasculature exhibit dramatic oscillations over the course of the day. Diurnal variations in the responsiveness of the cardiovascular system to environmental stimuli are mediated by a complex interplay between extracellular (i.e., neurohumoral factors) and intracellular (i.e., circadian clock) influences. The intracellular circadian clock is composed of a series of transcriptional modulators that together allow the cell to perceive the time of day, thereby enabling preparation for an anticipated stimulus. These molecular timepieces have been characterized recently within both vascular smooth muscle cells and cardiomyocytes, giving rise to a multitude of hypotheses relating to the potential role(s) of the circadian clock as a modulator of physiological and pathophysiological cardiovascular events. For example, evidence strongly supports the hypothesis that the circadian clock within the heart modulates myocardial metabolism, which in turn facilitates anticipation of diurnal variations in workload, substrate availability, and/or the energy supply-to-demand ratio. The purpose of this review is therefore to summarize our current understanding of the molecular events governing diurnal variations in the intrinsic properties of the heart, with special emphasis on the intramyocardial circadian clock. Whether impairment of this molecular mechanism contributes toward cardiovascular disease associated with hypertension, diabetes mellitus, shift work, sleep apnea, and/or obesity will be discussed.