ErbB2 is essential in the prevention of dilated cardiomyopathy

Steven A. Crone, You Yang Zhao, Lian Fan, Yusu Gu, Susumu Minamisawa, Yang Liu, Kirk L. Peterson, Ju Chen, Ronald Kahn, Gianluigi Condorelli, John Ross, Kenneth R. Chien, Kuo Fen Lee

Research output: Contribution to journalArticlepeer-review

653 Scopus citations

Abstract

Amplification of the gene encoding the ErbB2 (Her2/neu) receptor tyrosine kinase is critical for the progression of several forms of breast cancer. In a large-scale clinical trial, treatment with Herceptin (trastuzumab), a humanized blocking antibody against ErbB2, led to marked improvement in survival. However, cardiomyopathy was uncovered as a mitigating side effect, thereby suggesting an important role for ErbB2 signaling as a modifier of human heart failure. To investigate the physiological role of ErbB2 signaling in the adult heart, we generated mice with a ventricular-restricted deletion of Erbb2. These ErbB2-deficient conditional mutant mice were viable and displayed no overt phenotype. However, physiological analysis revealed the onset of multiple independent parameters of dilated cardiomyopathy, including chamber dilation, wall thinning and decreased contractility. Additionally, cardiomyocytes isolated from these conditional mutants were more susceptible to anthracycline toxicity. ErbB2 signaling in cardiomyocytes is therefore essential for the prevention of dilated cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)459-465
Number of pages7
JournalNature Medicine
Volume8
Issue number5
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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