Autophagy, Clock Genes, and Cardiovascular Disease.

Circadian rhythms are 24-hour cycles that regulate physical, mental, and behavioural changes of most living organisms. In the heart, circadian rhythms regulate processes such as heart rate, blood pressure, blood coagulability, and vascular tone. However, in addition to regulating physiologic processes, circadian rhythms regulate pathophysiologic processes in the heart. In this regard, circadian rhythms regulate the onset, severity, and outcome of many cardiovascular diseases (CVDs), including myocardial infarction, diabetic cardiomyopathy, doxorubicin (Dox)-induced cardiotoxicity, and heart failure. Notably, the underlying mechanism of many of these diseases is linked to impaired cellular quality control processes, such as autophagy. Autophagy is a homeostatic cellular process that regulates the removal of damaged cellular components, allowing their degradation and recycling into their basic constituents for production of cellular energy. Many studies from recent years point to a regulatory link between autophagy and circadian machinery in the control of CVDs. In this review, we highlight the recent discoveries in the field of circadian-induced autophagy in the heart and provide the molecular mechanisms and signalling pathways that underlie the crosstalk between autophagy and clock gene control in response to cardiac injury. Understanding the mechanisms that underlie circadian-induced autophagy in response to cardiac stress may prove to be beneficial in developing novel therapeutic approaches to treat cardiac disease.