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Updated: Jul 15, 2025

High Efficiency Differentiation of Human Pluripotent Stem Cells to Cardiomyocytes and Characterization by Flow Cytometry
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High Efficiency Differentiation of Human Pluripotent Stem Cells to Cardiomyocytes and Characterization by Flow Cytometry

Published on: September 23, 2014

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

Sobuj Mia1, Ravi Sonkar1, Lamario Williams1

  • 1Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.

JACC. Basic to Translational Science
|October 4, 2023
PubMed

Insights

Disrupting the cardiomyocyte circadian clock causes heart disease by increasing E4BP4. Blocking E4BP4 prevents this heart disease, revealing E4BP4 as a key regulator of cardiac health.

Area of Science:

  • Cardiovascular Biology
  • Chronobiology
  • Molecular Cardiology

Background:

  • Circadian clocks regulate essential daily biological functions, including cardiac metabolism and electrophysiology.
  • Disruption of the cardiomyocyte circadian clock is linked to age-onset heart disease through poorly understood mechanisms.

Purpose of the Study:

  • To investigate the molecular mechanisms linking cardiomyocyte circadian clock disruption to heart disease.
  • To identify novel regulators of cardiac physiology and pathophysiology.

Main Methods:

  • Genetic disruption of the cardiomyocyte circadian clock in a mouse model.
  • Analysis of gene expression, focusing on transcriptional repressors.
  • Assessment of cardiac function, metabolism, and electrophysiology.

Main Results:

  • Genetic disruption of the cardiomyocyte clock led to sustained E4BP4 (a transcriptional repressor) induction.
  • E4BP4 deletion abrogated age-onset cardiomyopathy following circadian clock disruption.
  • E4BP4 was found to regulate cardiac fatty acid oxidation and the QT interval.

Conclusions:

  • E4BP4 is a critical mediator linking circadian clock disruption to cardiac dysfunction.
  • E4BP4 plays a significant role in regulating cardiac metabolism and electrophysiology.
  • E4BP4 represents a novel therapeutic target for preventing or treating heart disease associated with circadian disruption.

Keywords:
chronobiologyelectrophysiologyheart failuremetabolism

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