Therapeutic Potential of REV-ERB Circadian Transcription Factors in Cardiac Function: A Comprehensive Review

Each aspect of physiology, from cardiovascular function to metabolism, varies throughout the day due to the influence of the circadian rhythms. There are significant molecular differences in the transcription, translation, signaling, and metabolism of the heart and other relevant tissues during the day and night. These fluctuations also impact the likelihood of adverse cardiovascular events, such as abnormal heartbeats and heart attacks. Because there are no effective treatments for heart failure, researchers are interested in targeting nuclear receptors, such as Rev-erbα/β, for use as drug therapies. Studies involving animal models have shown that activating REV-ERB can greatly reduce hypertrophy, fibrosis, and the progression of heart failure. Furthermore, the activation of REV-ERB with SR9009, an agonist, has been shown to restore cardiac function and decrease mortality following a heart attack. REV-ERBs regulate the circadian expression of genes, metabolism, and inflammatory processes, making them potential targets for cardiovascular diseases. The loss of REV-ERBs in mice has been linked to heart problems, highlighting the importance of these proteins in maintaining circadian rhythms and keeping the heart healthy. This article explores the essential role of REV-ERBα/β in cardiovascular disease, including its regulatory mechanisms and potential ligands for therapy. Raising NAD+ levels may help minimize disruption of the circadian clock and protect the heart. REV-ERBs may be targeted for the improvement of metabolism, inflammation, and overall cardiovascular health, although further research is necessary to fully elucidate how Rev-erbα/β ligand compounds could act as therapeutics for the molecular clock.