Abstract 1892: A Synthetic Peptide Derived from the Pro-Hormone of MGF Preserves Cardiac Function and Mobilizes Resident Stem Cell Populations Following Myocardial Infarction
IGF-I exists as two splice variants expressed in the heart, a predominant isoform IGF-IEa, and the other IGF-IEb, also known as mechano-growth factor (MGF). We found a significant increase in MGF splice variant expression 24 hours post-infarction (MGF, sham=.43±14 vs. MI=2.2±.43*, p<0.05, fg). Since MGF differs from IGF-IEa in the E-domain region of the pro-hormone, we are interested in determining whether the unique E-domain of MGF has a distinct biological function. To test this, a synthetic peptide corresponding to the E-domain of MGF was delivered systemically via mini-osmotic pumps at the time of myocardial infarction. Five groups of were studied: sham, sham+E-domain peptide (1mg/kg/day), MI, MI+ scrambled E-domain and MI+E-domain peptide. At 14-days post-infarct, pressure-volume analysis was performed and the hearts were removed for assessment of morphology, changes in gene expression and immunohistochemical staining performed. There was a 63% decrease in Emax and a 32% decrease in dP/dtmax, in the MI group, which was completely ameliorated in the MI+E-domain group. Other hemodynamic measures were also preserved in the MI+E-domain group, and significantly different compared to MI and MI+scrambled peptide groups. An increase in Hw/Bw ratio, ANF, β-MHC and MMP2 mRNA expression was inhibited in the MI+E-domain group. Immunohistochemical analysis revealed numerous small troponin I (TnI) positive cells that co-express both Nkx2.5 and islet-1 in myocardium of the E-domain treated mice. Analysis of the resident cardiac stem cell population in E-domain treated mice at 2 and 5 days, indicated an increase in the number of c-Kit+ and Sca-1+ cells suggesting that these cells may contribute to the appearance of the small TnI positive cells in the E-domain treated hearts. These data suggest that administration of the E-domain peptide derived from the pro-hormone form of IGF-I produced during injury, maybe used to facilitate the actions of IGF-I to improve cardiac function and mobilize resident stem cell populations.