The Cardiac Circadian Clock: Implications for Cardiovascular Disease and its Treatment

Abstract

Virtually all aspects of physiology fluctuate with respect to the time of day. This is beautifully exemplified by cardiovascular physiology, for which blood pressure and electrophysiology exhibit robust diurnal oscillations. At molecular/biochemical levels (eg, transcription, translation, signaling, metabolism), cardiovascular-relevant tissues (such as the heart) are profoundly different during the day vs the night. Unfortunately, this in turn contributes toward 24-hour rhythms in both risk of adverse event onset (eg, arrhythmias, myocardial infarction) and pathogenesis severity (eg, extent of ischemic damage). Accumulating evidence indicates that cell-autonomous timekeeping mechanisms, termed circadian clocks, temporally govern biological processes known to play critical roles in cardiovascular function/dysfunction. In this paper, a comprehensive review of our current understanding of the cardiomyocyte circadian clock during both health and disease is detailed. Unprecedented basic, translational, and epidemiologic studies support a need to implement chronobiological considerations in strategies designed for both prevention and treatment of cardiovascular disease.

Keywords: chronobiology; electrophysiology; heart failure; ischemia; metabolism.