Search

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 the potential therapeutic benefits of IGF-1 on cardiac function using an in vivo model of chronic catecholamine-induced cardiomyopathy. Methods Rats were perfused with isoproterenol via osmotic pump (1 mg kg−1 per day) and treated with 2 mg kg−1 IGF-1 (2 mg kg−1 per day, 6 days a week) for 2 or 4 weeks. Echocardiography, ECG, and blood pressure were assessed. In vivo pressure-volume loop studies were conducted at 4 weeks. Heart sections were analysed for fibrosis and apoptosis, and relevant biochemical signalling cascades were assessed. Results After 4 weeks, diastolic function ( EDPVR, EDP, tau, E/A ratio), systolic function ( PRSW, ESPVR, dP/dtmax) and structural remodelling ( LV chamber diameter, wall thickness) were all adversely affected in isoproterenol-treated rats. All these detrimental effects were attenuated in rats treated with Iso+ IGF-1. Isoproterenol-dependent effects on BP were attenuated by IGF-1 treatment. Adrenergic sensitivity was blunted in isoproterenol-treated rats but was preserved by IGF-1 treatment. Immunoblots indicate that cardioprotective p110 α signalling and activated Akt are selectively upregulated in Iso+ IGF-1-treated hearts. Expression of iNOS was significantly increased in both the Iso and Iso+ IGF-1 groups; however, tetrahydrobiopterin ( BH4) levels were decreased in the Iso group and maintained by IGF-1 treatment. Conclusion IGF-1 treatment attenuates diastolic and systolic dysfunction associated with chronic catecholamine-induced cardiomyopathy while preserving adrenergic sensitivity and promoting BH4 production. These data support the potential use of IGF-1 therapy for clinical applications for cardiomyopathies. [ABSTRACT FROM AUTHOR]