Journal of molecular and cellular cardiologySep 4, 2025

Daily rhythm regulators REV-ERBα/β and E4BP4 control heart function

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Circadian repressors REV-ERB alpha/beta and E4BP4 may help regulate cardiac gene programs, metabolism, and disease-linked heart function.

Evidence

This review discusses studies on REV-ERBs and E4BP4 in healthy and diseased hearts, including mechanisms tied to cardiac gene expression and metabolism.

Caveat

The therapeutic claim remains prospective because the abstract does not report a new cardiovascular intervention trial or clinical outcomes.

Simplified

Circadian rhythms are an endogenous timekeeping system with a period of approximately 24 h that regulate many aspects of body physiology to maintain organismal health. Dysregulation of circadian rhythmicity has been implicated in various human diseases such as cancer as well as metabolic and cardiovascular disorders. Intrinsic, biological oscillations are regulated by the circadian clock, a molecular transcriptional/translational feedback loop that involves activators such as BMAL1 and CLOCK, and repressors such as REV-ERBα/β and E4BP4. Recent studies have shown that REV-ERBs and E4BP4 play a key role in regulating cardiac gene expression programs and metabolism. Here, we discuss these findings and highlight the mechanisms of their role in healthy and diseased hearts. Since REV-ERBs are drug targets, they hold potential for the treatment of cardiovascular disorders that are linked to circadian dysregulation or metabolic imbalance.