Insulin-like growth factor 1 prevents diastolic and systolic dysfunction associated with cardiomyopathy and preserves adrenergic sensitivity.

摘要: Aims Insulin-like growth factor 1 (IGF-1)-dependent signalling promotes exercise-induced physiological cardiac hypertrophy. However, the in vivo therapeutic potential of IGF-1 for heart disease is not well established. Here, we test benefits on function using an model chronic catecholamine-induced cardiomyopathy. Methods Rats were perfused with isoproterenol via osmotic pump (1 mg kg−1 per day) and treated 2 mg kg−1 (2 mg kg−1 day, 6 days a week) 2 or 4 weeks. Echocardiography, ECG, blood pressure assessed. In vivo pressure–volume loop studies conducted at Heart sections analysed fibrosis apoptosis, relevant biochemical cascades assessed. Results After 4 weeks, diastolic (EDPVR, EDP, tau, E/A ratio), systolic (PRSW, ESPVR, dP/dtmax) structural remodelling (LV chamber diameter, wall thickness) all adversely affected in isoproterenol-treated rats. All these detrimental effects attenuated rats Iso+IGF-1. Isoproterenol-dependent BP by treatment. Adrenergic sensitivity was blunted but preserved Immunoblots indicate that cardioprotective p110α activated Akt are selectively upregulated Iso+IGF-1-treated hearts. Expression iNOS significantly increased both Iso Iso+IGF-1 groups; however, tetrahydrobiopterin (BH4) levels decreased group maintained treatment. Conclusion IGF-1 treatment attenuates dysfunction associated cardiomyopathy while preserving adrenergic promoting BH4 production. These data support use therapy clinical applications cardiomyopathies.