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Updated: Jun 21, 2026
Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
Published on: September 27, 2012
Anticipating anticipation: pursuing identification of cardiomyocyte circadian clock function
1USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Dept. of Pediatrics, 1100 Bates St., Houston, TX 77030, USA. meyoung@bcm.edu
Insights
The heart has an internal circadian clock within its cells that influences heart function and disease. Disrupting this cardiomyocyte circadian clock impacts cardiovascular health, opening new avenues for treatment.
Area of Science:
- Cardiovascular Physiology
- Chronobiology
- Molecular Cardiology
Background:
- Diurnal rhythms affect heart function and disease, traditionally attributed to external factors.
- Recent evidence reveals an intrinsic cardiomyocyte circadian clock within heart cells.
- This intracellular clock anticipates environmental changes, optimizing cellular responses.
Purpose of the Study:
- To review current knowledge on the cardiomyocyte circadian clock's role in cardiovascular physiology and pathophysiology.
- To highlight emerging research frontiers in understanding and targeting this mechanism.
- To explore the implications for cardiovascular disease prevention and treatment.
Main Methods:
- Review of existing literature on cardiomyocyte circadian clocks.
- Analysis of studies using genetically modified mice with disrupted cardiomyocyte clocks.
- Discussion of ongoing and future research directions.
Main Results:
- The cardiomyocyte circadian clock regulates gene expression, beta-adrenergic signaling, and metabolism.
- It influences heart rate, cardiac output, and tolerance to ischemia-reperfusion.
- Disruption of this clock has significant pathophysiological consequences.
Conclusions:
- The cardiomyocyte circadian clock is a critical regulator of heart function and disease.
- Future research should focus on molecular links, pathophysiological impacts, and therapeutic targeting.
- Understanding this clock may offer novel strategies for cardiovascular disease management and potentially benefit other tissues.
Abstract:
Diurnal rhythms in myocardial physiology (e.g., metabolism, contractile function) and pathophyiology (e.g., sudden cardiac death) are well establish and have classically been ascribed to time-of-day-dependent alterations in the neurohumoral milieu. Existence of an intramyocellular circadian clock has recently been exposed. Circadian clocks enable the cell to anticipate environmental stimuli, facilitating a timely and appropriate response. Generation of genetically modified mice with a targeted disruption of the cardiomyocyte circadian clock has provided an initial means for deciphering the functions of this transcriptionally based mechanism and allowed predictions regarding which environmental stimuli the heart anticipates (i.e., "anticipating anticipation"). Recent studies show that the cardiomyocyte circadian clock influences myocardial gene expression, beta-adrenergic signaling, transcriptional responsiveness to fatty acids, triglyceride metabolism, heart rate, and cardiac output, as well as ischemia-reperfusion tolerance. In addition to reviewing current knowledge regarding the roles of the cardiomyocyte circadian clock, this article highlights putative frontiers in this field. The latter includes establishing molecular links between the cardiomyocyte circadian clock with identified functions, understanding the pathophysiological consequences of disruption of this mechanism, targeting resynchronization of the cardiomyocyte circadian clock for prevention/treatment of cardiovascular disease, linking the circadian clock with the cardiobeneficial effects of caloric restriction, and determining whether circadian clock genes are subject to epigenetic regulation. Information gained from studies investigating the cardiomyocyte circadian clock will likely translate to extracardiac tissues, such as skeletal muscle, liver, and adipose tissue.
