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

Circ Res. 2002 Apr 5;90(6):641-8. doi: 10.1161/01.res.0000013780.77774.75.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Calcium / metabolism
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / physiopathology*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Cell Count
  • Cell Size
  • Gene Expression Regulation*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / physiology*
  • Ki-67 Antigen / biosynthesis
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins*
  • Tropomodulin
  • Ventricular Remodeling / genetics


  • Carrier Proteins
  • Ki-67 Antigen
  • Microfilament Proteins
  • Tmod1 protein, mouse
  • Tropomodulin
  • Insulin-Like Growth Factor I
  • Calcium