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

S R Roof1, J Boslett2, D Russell3

  • 1Q-Test Labs, Columbus, OH, USA.

Acta Physiologica (Oxford, England)
|September 25, 2015
PubMed

Insights

Insulin-like growth factor 1 (IGF-1) therapy improved heart function in a rat model of cardiomyopathy. IGF-1 treatment attenuated detrimental effects of catecholamine exposure, preserving cardiac function and adrenergic sensitivity.

Area of Science:

  • Cardiovascular Research
  • Endocrinology
  • Pharmacology

Background:

  • Insulin-like growth factor 1 (IGF-1) signaling is known to promote exercise-induced cardiac hypertrophy.
  • The therapeutic potential of IGF-1 for heart disease in vivo remains incompletely understood.
  • Chronic catecholamine exposure can induce cardiomyopathy, a significant cardiovascular condition.

Purpose of the Study:

  • To investigate the therapeutic benefits of IGF-1 on cardiac function in an established in vivo model of chronic catecholamine-induced cardiomyopathy.
  • To assess the impact of IGF-1 on both systolic and diastolic cardiac dysfunction.
  • To evaluate IGF-1's effects on adrenergic sensitivity and underlying molecular signaling pathways.

Main Methods:

  • Rats were administered isoproterenol to induce cardiomyopathy and treated with IGF-1.
  • Cardiac function was assessed using echocardiography, ECG, blood pressure measurements, and in vivo pressure-volume loop studies.
  • Histological analysis for fibrosis and apoptosis, alongside biochemical assessments of signaling cascades, were performed.

Main Results:

  • Isoproterenol treatment led to significant diastolic and systolic dysfunction, alongside adverse structural remodeling.
  • IGF-1 treatment attenuated these detrimental effects, improving cardiac function and preserving adrenergic sensitivity.
  • IGF-1 upregulated cardioprotective p110α/Akt signaling and maintained tetrahydrobiopterin (BH4) levels, which were reduced by isoproterenol alone.

Conclusions:

  • IGF-1 therapy effectively attenuates cardiac dysfunction in a model of catecholamine-induced cardiomyopathy.
  • The treatment preserves adrenergic sensitivity and promotes beneficial signaling pathways, including BH4 production.
  • These findings support the potential clinical application of IGF-1 for treating cardiomyopathies.
Abstract

Keywords:
adrenergic stimulationcardiomyopathydiastolic dysfunctioninsulin-like growth factor 1systolic dysfunctiontetrahydrobiopterin

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