Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice

Sara Welch, David Plank, Sandra Witt, Betty Glascock, Erik Schaefer, Stefano Chimenti, Anna Maria Andreoli, Federica Limana, Annarosa Leri, Jan Kajstura, Piero Anversa, Mark A. Sussman

Research output: Contribution to journalArticle

Abstract

To test the hypothesis that early interventional treatment with insulin-like growth factor-1 (IGF-1) alleviates subsequent development of dilated cardiomyopathy, cardiac-specific IGF-1 expression was introduced by selective cross-breeding into a transgenic mouse model of heart failure that displays phenotypic characteristics of severe dilation, Hemodynamic, structural, and cellular parameters of the heart were compared between nontransgenic, tropomodulin-overexpressing cardiomyopathic, and the hybrid tropomodulin/IGF-1-overexpressing mice. Beneficial effects of IGF-1 were apparent by multiple indices of cardiac structure and function, including normalization of heart mass, anatomy, hemodynamics, and apoptosis, IGF-1 expression also acted as a proliferative stimulus as evidenced by calculated increases in myocyte number as well as expression of Ki67, a nuclear marker of cellular replication, Cellular analyses revealed that IGF-1 inhibited characteristic cardiomyocyte elongation in dilated hearts and restored calcium dynamics comparable to that observed in normal cells. Collectively, these results provide novel information regarding the ability of IGF-1 to inhibit progression of cardiomyopathic disease in a defined model system and suggest that heart failure may benefit from early interventional IGF-1 treatment.

Original languageEnglish
Pages (from-to)641-648
Number of pages8
JournalCirculation Research
Volume90
Issue number6
DOIs
Publication statusPublished - Apr 5 2002

Keywords

  • Dilated cardiomyopathy
  • Heart
  • Insulin-like growth factor
  • Transgenic

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Welch, S., Plank, D., Witt, S., Glascock, B., Schaefer, E., Chimenti, S., Andreoli, A. M., Limana, F., Leri, A., Kajstura, J., Anversa, P., & Sussman, M. A. (2002). Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice. Circulation Research, 90(6), 641-648. https://doi.org/10.1161/01.RES.0000013780.77774.75