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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)1141-1156
Number of pages16
JournalJACC: Basic to Translational Science
Volume8
Issue number9
DOIs
StatePublished - Sep 2023

Keywords

  • chronobiology
  • electrophysiology
  • heart failure
  • metabolism

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