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Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation
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Anti-erbB2 treatment induces cardiotoxicity by interfering with cell survival pathways

Thea Pugatsch1, Suzan Abedat, Chaim Lotan

  • 1The Cardiovascular Research Center, Heart Institute, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. pthea@hadassah.org.il

Breast Cancer Research : BCR
|July 15, 2006
PubMed
Abstract

Insights

Blocking ErbB-2 with the B-10 antibody in rat heart cells disrupts cardiomyocyte function, reduces contractility, and induces apoptosis, potentially impairing cardiac stress response.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Oncology

Background:

  • Cardiac dysfunction is a serious side effect of anti-erbB2 monoclonal antibody therapy.
  • The ErbB-2 pathway is crucial for cardiomyocyte survival and function.
  • Targeting ErbB-2 in cancer therapy may inadvertently affect cardiac cells.

Purpose of the Study:

  • To investigate the effects of the anti-erbB2 antibody B-10 on rat cardiomyocytes.
  • To determine the molecular and functional consequences of ErbB-2 pathway blockade in heart cells.

Main Methods:

  • Primary rat cardiomyocyte cultures were treated with the B-10 antibody.
  • Gene expression analyzed by RT-PCR and microarray.
  • Protein levels assessed by Western blot; contractility by video motion analysis; calcium transients by FURA; apoptosis by TUNEL assay.

Main Results:

  • B-10 altered expression of 24 stress-related genes.
  • ErbB-2, ErbB-3, ErbB-4, and neuregulin protein levels decreased; ErbB-4 and gp130 increased.
  • Overexpression of calreticulin and calsequestrin reduced calcium transients, impaired contractility, and induced apoptosis in 20% of cells.

Conclusions:

  • Blocking ErbB-2 in cardiomyocytes alters cell cycle and genes involved in heart function.
  • B-10 inhibits pro-survival pathways and reduces cellular contractility.
  • These effects suggest a potential impairment of the heart's stress response.

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