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

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.

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.

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.

We conclude that the E domain of MGF protects the myocardium against ischaemia, thus improving cardiac function post-MI.