Mechano-growth factor reduces loss of cardiac function in acute myocardial infarction.

Abstract

BACKGROUND: Mechano-growth factor (MGF) is a splice-variant of IGF-I sharing an identical mature region, but with a different E domain. Our objective was to determine if MGF would reduce the area of 'at-risk' myocardium and improve cardiac function in the post-infarct heart. METHODS: Infarcts were induced by injection of microspheres. In experiment 1, sheep were treated with vehicle, 200 nM each of mature IGF-I, MGF E domain, or full-length MGF. In experiment 2, sheep were treated with vehicle or 200 nM of MGF E domain alone. Cardiac function was assessed using echocardiography and sheep were killed eight days post-MI. Evans Blue dye was injected before death to stain the compromised myocardium. Immunohistochemistry was used to assess the abundance of pAkt(T308) and cleaved caspase 3. RESULTS: In experiment 1, cardiac function improved in sheep treated with the MGF E domain, while in experiment 2, MGF E domain preserved cardiac function and there was 35% less compromised cardiac muscle than controls. Furthermore, immunostaining of cleaved caspase 3 was absent in MGF E domain-treated hearts, suggesting that MGF E domain reduced infarct expansion. CONCLUSIONS: We conclude that the E domain of MGF protects the myocardium against ischaemia, thus improving cardiac function post-MI.