RGD Reference Report - Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice. - Rat Genome Database

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

Authors: Welch, S  Plank, D  Witt, S  Glascock, B  Schaefer, E  Chimenti, S  Andreoli, AM  Limana, F  Leri, A  Kajstura, J  Anversa, P  Sussman, MA 
Citation: Welch S, etal., Circ Res. 2002 Apr 5;90(6):641-8.
RGD ID: 1598419
Pubmed: PMID:11934830   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dilated cardiomyopathy  IDA 1598419 RGD 
dilated cardiomyopathy  ISOIGF1 (Homo sapiens)1598419; 1598419 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1  (insulin-like growth factor 1)

Genes (Mus musculus)
Igf1  (insulin-like growth factor 1)

Genes (Homo sapiens)
IGF1  (insulin like growth factor 1)


Additional Information