Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology 
and Pathophysiology

Mia, Sobuj; Sonkar, Ravi; Williams, Lamario; Latimer, Mary N.; Rawnsley, David R.; Rana, Samir; He, Jin; Dierickx, Pieterjan; Kim, Teayoun; Xie, Min; Habegger, Kirk M.; Kubo, Masato; Zhou, Lufang; Thomsen, Morten B.; Prabhu, Sumanth D.; Frank, Stuart J.; Brookes, Paul S.; Lazar, Mitchell A.; Diwan, Abhinav; Young, Martin E.

doi:10.1016/j.jacbts.2023.03.016

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Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology

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Dierickx, Pieterjan
Circadian Regulation of Cardiometabolism, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Citation

Mia, S., Sonkar, R., Williams, L., Latimer, M. N., Rawnsley, D. R., Rana, S., et al. (2023). Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology. JACC-BASIC TO TRANSLATIONAL SCIENCE, 8(9), 1141-1156. doi:10.1016/j.jacbts.2023.03.016.

Cite as: https://hdl.handle.net/21.11116/0000-000D-E7BA-D

Abstract

Circadian clocks temporally orchestrate biological processes critical for cellular/organ function. For example, the cardiomyocyte circadian clock modulates cardiac metabolism, signaling, and electrophysiology over the course of the day, such that, disruption of the clock leads to age-onset cardiomyopathy (through unknown mechanisms). Here, we report that genetic disruption of the cardiomyocyte clock results in chronic induction of the transcriptional repressor E4BP4. Importantly, E4BP4 deletion prevents age-onset cardiomyopathy following clock disruption. These studies also indicate that E4BP4 regulates both cardiac metabolism (eg, fatty acid oxidation) and electrophysiology (eg, QT interval). Collectively, these studies reveal that E4BP4 is a novel regulator of both cardiac physiology and pathophysiology. (J Am Coll Cardiol Basic Trans Science 2023;8:1141-1156) (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).