| First Author | Welch S | Year | 2002 |
| Journal | Circ Res | Volume | 90 |
| Issue | 6 | Pages | 641-8 |
| PubMed ID | 11934830 | Mgi Jnum | J:128671 |
| Mgi Id | MGI:3767767 | Doi | 10.1161/01.res.0000013780.77774.75 |
| Citation | Welch S, et al. (2002) Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice. Circ Res 90(6):641-8 |
| abstractText | 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. |
