title: Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.
abstract: IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI.
authors.affiliation: Wallenberg Laboratory at Sahlgrenska Academy, Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Scharin Täng
authors.forename: B
authors.initials: B
authors.lastname: Redfors
authors.forename: M
authors.initials: M
authors.lastname: Lindbom
authors.forename: J
authors.initials: J
authors.lastname: Svensson
authors.forename: T
authors.initials: T
authors.lastname: Ramunddal
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Y
authors.initials: Y
authors.lastname: Shao
authors.forename: E
authors.initials: E
authors.lastname: Omerovic
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010725:Phosphocreatine / Q000378:metabolism; D014463:Ultrasonography; D020257:Ventricular Remodeling
chemical_list: C519530:insulin-like growth factor-1, mouse; D010725:Phosphocreatine; D007334:Insulin-Like Growth Factor I