Targeting circadian PER2 as therapy in myocardial ischemia and reperfusion injury

ABSTRACT

The cycle of day and night dominates life on earth. Therefore, almost all living organisms adopted a molecular clock linked to the light-dark cycles. It is now well established that this molecular clock is crucial for human health and wellbeing. Disruption of the molecular clockwork directly results in a myriad of disorders, including cardiovascular diseases. Further, the onset of many cardiovascular diseases such as acute myocardial infarction exhibits a circadian periodicity with worse outcomes in the early morning hours. Based on these observations, the research community became interested in manipulating the molecular clock to treat cardiovascular diseases. In recent years, several exciting discoveries of pharmacological agents or molecular mechanisms targeting the molecular clockwork have paved the way for circadian medicine’s arrival in cardiovascular diseases. The current review will outline the most recent circadian therapeutic advances related to the circadian rhythm protein Period2 (PER2) to treat myocardial ischemia and summarize future research in the respective field.

KEYWORDS:

• Per2
• circadian
• intense light
• amplitude enhancement
• myocardial ischemia
• anticoagulation
• micro-RNA
• adenosine
• nobiletin
• inflammation
• SR9009
• miR-21

Additional information

Funding

This work was supported by the American Heart Association (AHA) Postdoctoral Fellowship 19POST34380105 to YO and the National Heart, Lung, and Blood Institute (NIH-NHLBI) [5R01HL122472] TE.