Résumé :
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Communication n° 202 Introduction : As cardiac disorders are a common complication in neuromuscular disorders, it seems essential to treat both skeletal and cardiac muscles in these pathologies. 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. Objectives : The hamster strain CHF147, that displays a progressive cardiomyopathy leading to heart failure, has been used to test whether stimulation of a hypertrophic pathway could delay the process of dilatation and better preserves the cardiac function. Insulin-like Growth Factor (IGF-1) is known to play a key role in cardiac function and cardiac growth and its administration has been shown to cause hypertrophy in normal hearts. Methods : Six month old CHF147 hamsters were treated with IGF-1 and we compared the efficacy of systemic administration of human recombinant IGF-1 protein (rh IGF-1) at a low dose to that of direct myocardial injection of plasmid DNA containing IGF-1 cDNA (pCMV-IGF1). Results : IGF-1 treatment did not induce a significant variation of ventricle mass, but preserved left ventricular 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 non-treated hamsters and also a trend towards increased contractility. Conclusion : This study provides evidence that IGF-1 treatment induces beneficial structural and functional effects on DCM of CHF147 hamsters. However, systemic administration of IGF-1 leading to high serum levels may induce a specific cardiomyopathy with impaired cardiac function and could even be linked with an increased risk of cancer. Thus, a gene therapy approach using IGF-1 in the treatment of heart failure due to DCM seems to be more adapted.
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