Short-term treatment using insulin-like growth factor-1 (IGF-1) improves life expectancy of the delta-sarcoglycan deficient hamster.

BACKGROUND: The hamster strain CHF147 presents a progressive dilated cardiomyopathy (DCM) due to a large deletion of the delta-sarcoglycan gene that leads to heart failure. This cardiomyopathy induces premature death. We have previously shown that a short-term treatment using IGF-1 preserves cardiac structure and improves function of the CHF147 hamster. METHODS: In the current study, we measured long-term effects of short-term treatment with recombinant human IGF-1 (rhIGF-1) in CHF147 hamsters. CHF147 hamsters (7-8 months old) were implanted under the skin with an osmotic pump filled either with saline or with recombinant human IGF-1 at a total dose of 25 microg. The osmotic pump allowed a continuous delivery of the protein for a mean duration of 19 days. RESULTS: We observed a significant increase in overall survival, as well as preservation of cardiac function, in the rhIGF-1-treated group. At the time of death, hearts of treated animals did not present any macroscopical or histological differences compared to those of sham hamsters. These results show that rhIGF-1 treatment slows down the evolution of the DCM in the CHF147 hamster. Moreover, the low dose treatment did not increase IGF-1 serum levels. CONCLUSIONS: This study is the first one reporting beneficial effects of IGF-1 treatment on survival of an animal model presenting DCM. Our results raise hopes for a new therapeutic approach of this pathology.

Administration of insulin-like growth factor-1 (IGF-1) improves both structure and function of delta-sarcoglycan deficient cardiac muscle in the hamster.

Dilated cardiomyopathies (DCM) are due to progressive dilatation of the cardiac cavities and thinning of the ventricular walls and lead unavoidably to heart failure. They represent a major cause for heart transplantation and, therefore, defining an efficient symptomatic treatment for DCM remains a challenge. We have taken advantage of the hamster strain CHF147 that displays progressive cardiomyopathy leading to heart failure to test whether stimulation of a hypertrophic pathway could delay the process of dilatation.Six month old CHF147 hamsters were treated with IGF-1 so that we could compare the efficacy of systemic administration of human recombinant IGF-1 protein (rh IGF-1) at low dose to that of direct myocardial injections of a plasmid DNA containing IGF-1 cDNA (pCMV-IGF1).IGF-1 treatment did not induce a significant variation of ventricle mass, but preserved left ventricular (LV) wall thickness and delayed dilatation of cardiac cavities when compared to non-treated hamsters. Together with this reduction of dilatation, we also noted a reduction in the amount of interstitial collagen. Furthermore, IGF-1 treatment induced beneficial effects on cardiac function since treated hamsters presented improved cardiac output and stroke volume, decreased end diastolic pressure when compared to nontreated hamsters and also showed a trend towards increased contractility (dP/dt(max)).This study provides evidence that IGF-1 treatment induces beneficial structural and functional effects on DCM of CHF147 hamsters, hence making this molecule a promising candidate for future gene therapy of heart failure due to DCM.