title: Administration of insulin-like growth factor-1 (IGF-1) improves both structure and function of delta-sarcoglycan deficient cardiac muscle in the hamster.
abstract: 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.
authors.affiliation: Institute de myologie - Inserm U582, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Serose
authors.forename: Bernard
authors.initials: B
authors.lastname: Prudhon
authors.forename: André
authors.initials: A
authors.lastname: Salmon
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Doyennette
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Fiszman
authors.forename: Yves
authors.initials: Y
authors.lastname: Fromes
mesh_terms: D000818:Animals; D002302:Cardiac Output; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D004195:Disease Models, Animal; D005355:Fibrosis; D015316:Genetic Therapy; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D049031:Sarcoglycans / Q000172:deficiency* / Q000235:genetics; D013318:Stroke Volume; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D002316:Cardiotonic Agents; D011994:Recombinant Proteins; D049031:Sarcoglycans; D007334:Insulin-Like Growth Factor I; D003094:Collagen