Mechano-growth factor reduces loss of cardiac function in acute myocardial infarction.
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.
Carpenter
Violaine
V
Waikato Clinical School, Private Bag 3200, Hamilton, New Zealand.
Matthews
Kenneth
K
Devlin
Gerard
G
Stuart
Selwyn
S
Jensen
Juliet
J
Conaglen
John
J
Jeanplong
Ferenc
F
Goldspink
Paul
P
Yang
Shi-Yu
SY
Goldspink
Geoffrey
G
Bass
James
J
McMahon
Christopher
C
D000818:Animals; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D006334:Heart Function Tests; D006439:Hemodynamics / Q000502:physiology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D012756:Sheep; D013318:Stroke Volume; D020257:Ventricular Remodeling / Q000187:drug effects*
D007334:Insulin-Like Growth Factor I