Circadian regulation of cardiac muscle function and protein degradation

ABSTRACT

The circadian clock plays a fundamental role in physiology. In particular, the heart is a target organ where the clock orchestrates various aspects of cardiac function. At the molecular level, the clock machinery governs daily rhythms of gene expression. Such circadian regulation is in tune with the dynamic nature of heart structure and function, and provides the foundation for chronotherapeutic applications in cardiovascular diseases. In comparison, a regulatory role of the clock in cardiac protein degradation is poorly documented. Sarcomere is the structural and functional unit responsible for cardiac muscle contraction, and sarcomere components are closely regulated by protein folding and proteolysis. Emerging evidence supports a role of the circadian clock in governing sarcomere integrity and function. Particularly, recent studies uncovered a circadian regulation of a core sarcomere component TCAP. It is possible that circadian regulation of the cardiac muscle protein turnover is a key regulatory mechanism underlying cardiac remodeling in response to physiological and environmental stimuli. While the detailed regulatory mechanisms and the molecular links to cardiac (patho)physiology remain to be further studied, therapeutic strategies targeting circadian control in the heart may markedly enhance intervention outcomes against cardiovascular disease.

KEYWORDS:

• Circadian clock
• heart
• sarcomere
• protein degradation
• chronotherapy

Acknowledgements

I thank Zheng Chen for discussion. Circadian research in my lab is in part supported by The Welch Foundation (AU-1971-20180324), NIH/NIGMS (R01GM114424) and NIH/NIA (R03AG063286) to S.-H.Y.

Additional information

Funding

This work was supported by the National Institute on Aging [R03AG063286]; National Institutes of Health [R01GM114424].