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Updated: Jun 23, 2026

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
08:09

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

Progressive suppression of DNA repair genes with persistent p53 target activation in doxorubicin-treated

Emma M Pfortmiller1, José A Gutiérrez2, Alyssa R Bogar2

  • 1Pharmacology and Toxicology Graduate Program, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, United States.

G3 (Bethesda, Md.)
|June 22, 2026
PubMed

Insights

Doxorubicin causes cardiotoxicity by damaging DNA in heart cells. This study reveals long-term gene expression changes, identifying potential biomarkers and therapeutic targets for doxorubicin-induced cardiotoxicity.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genomics

Background:

  • Doxorubicin (DOX) is a potent anticancer agent.
  • DOX-induced cardiotoxicity (DIC) poses a significant clinical challenge, often manifesting years after treatment.
  • Current in vitro models primarily capture acute DOX effects, neglecting long-term consequences.

Purpose of the Study:

  • To investigate the chronic gene expression alterations in cardiomyocytes following doxorubicin exposure.
  • To identify molecular signatures associated with long-term doxorubicin-induced cardiotoxicity.
  • To explore potential therapeutic targets and biomarkers for DIC.

Main Methods:

  • Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from six individuals were treated with DOX for 24 hours.
  • Global gene expression profiling was performed at 0, 24, and 144 hours post-treatment recovery.
  • DNA damage was assessed via γH2AX expression.

Main Results:

  • DOX induced DNA double-strand breaks, which were resolved by 144 hours of recovery.
  • Distinct acute and chronic gene expression signatures were identified.
  • The chronic signature (501 genes) was enriched for p53 target genes, DNA damage response (DDR) genes, and senescence-associated genes.
  • p53 target genes remained persistently activated, while DDR genes showed progressive downregulation.

Conclusions:

  • Doxorubicin exposure induces a lasting altered cellular state in cardiomyocytes, even after DNA repair.
  • Persistent gene expression changes offer potential targets for mitigating doxorubicin cardiotoxicity.
  • This study provides a foundation for developing novel biomarkers and therapeutics for DIC.
Keywords:
CardiomyocytesDNA damageDoxorubicinGlobal gene expression

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