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.
Serose
Armelle
A
Institute de myologie - Inserm U582, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Prudhon
Bernard
B
Salmon
André
A
Doyennette
Marie-Agnès
MA
Fiszman
Marc Y
MY
Fromes
Yves
Y
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
D002316:Cardiotonic Agents; D011994:Recombinant Proteins; D049031:Sarcoglycans; D007334:Insulin-Like Growth Factor I; D003094:Collagen