Peripheral Circadian Clocks in the Vasculature

Abstract

Abstract-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. (Arterioscler Thromb Vasc Biol. 2007;27:1694-1705.)ircadian rhythms are daily cycles of physiology and behavior that are driven by an endogenous oscillator with a period of approximately (circa-) one day (dies). 1 The most obvious circadian rhythm in humans is the cycle of sleep and wakefulness. 2 These cycles are not simply consequences of light perception, but are generated by endogenous circadian clocks that can adapt the physiology of an organism to its needs in an anticipatory manner. Their expression continues (free-runs) when subjects are isolated from the light cycle, with the oscillator defining predicted day and night, organizing our behavior and physiology appropriately to adapt to the contrasting demands encountered throughout the 24-hour period.Cardiovascular or hemodynamic parameters such as heart rate, blood pressure, endothelial function, and fibrinolytic activity exhibit variations consistent with circadian rhythm. Additionally, several types of acute pathological cardiac events exhibit diurnal patterns. The incidence of acute myocardial infarction, myocardial ischemia, cardiac arrest, ventricular tachycardia, post myocardial infarction, and sudden death in heart failure all vary according to the time of day. 3,4 Social and commercial pressures such as shift work, which oppose the temporal circadian order, may be underlying factors contributing to the incidence of chronic illnesses such as cardiovascular disease and cancer. 5,6 Understanding this molecular clock and its mechanisms may ultimately allow treatment of conditions where either the severity of the illness or therapeutic efficacy exhibit circadian rhythmicity. Molecular Basis of Circadian ClocksCircadian rhythms are regulated by three components: (1)...

Impact of the human circadian system, exercise, and their interaction on cardiovascular function

“…The potential underlying mechanisms of the circadian variation in cardiovascular biomarkers may include humoral circadian rhythms driven by the SCN (e.g., ACTH), multisynaptic neural projections from the SCN to the organs (e.g., heart, vasculature, and adrenal gland), and/or peripheral oscillators located in these organs (13,19,20). Circadian rhythms in autonomic nervous system activity and humoral factors, in turn, could contribute to synchronization of peripheral oscillators in the heart and vasculature (21,22). Surprisingly, we also found evidence for the existence of endogenous ≈12-h rhythm in cardiovascular biomarkers, specifically in platelet aggregability and in the reactivity to exercise of epinephrine and norepinephrine.…”

Between a ROCK and a Hard Place

“…6 Coincident with the diurnal pattern of cardiovascular events, diurnal variations have been reported in the pressor response to infused vasoconstrictors, sympathetic nerve activity, the renin-angiotensin system, QT interval, plasma fibrinolytic activity, platelet aggregability, and vascular contractility [7][8][9][10][11][12] ( Figure). Nocturnal mammals, including the mouse, are most active at night, and their circadian rhythms in activity and cardiovascular function are flipped-antiphase to those observed in humans (Figure).…”

Non-Ultradian Cardiac Rhythms: Circadian Regulation of the Heart

“…Heart rate (HR) and blood pressure (BP) both exhibit diurnal rhythms in humans, peaking the during the day when humans are active, or during the active nocturnal phase in rodent models (Mansoor et al, 1994;Millar-Craig et al, 1978;Reilly et al, 2007;Weber et al, 2002). HR and BP are lowest during nighttime, but begin to rise in the early morning hours in anticipation of waking.…”