Insulin like growth factor-I (IGF-1)
isoforms differ structurally in their E-domain regions and their temporal expression profile in response to injury. We and others have reported that Mechano-
growth factor (MGF), which is equivalent to human IGF-1c and rodent IGF-1Eb
isoforms, is expressed acutely following
myocardial infarction (MI) in the mouse heart. To examine the function of the E-domain region, we have used a stabilized synthetic
peptide analog corresponding to the unique 24
amino acid region E-domain of MGF. Here we deliver the human MGF
E-domain peptide to mice during the acute phase (within 12 hours) and the chronic phase (8 weeks) post-MI. We assessed the impact of
peptide delivery on cardiac function and cardiovascular hemodynamics by pressure-volume (P-V) loop analysis and gene expression by quantitative RT-PCR. A significant decline in both systolic and diastolic hemodynamics accompanied by pathologic
hypertrophy occurred by 10 weeks post-MI in the untreated group. Delivery of the
E-domain peptide during the acute phase post-MI ameliorated the decline in hemodynamics, delayed decompensation but did not prevent pathologic
hypertrophy. Delivery during the chronic phase post-MI significantly improved systolic function, predominantly due to the effects on vascular resistance and prevented decompensation. While pathologic
hypertrophy persisted there was a significant decline in
atrial natriuretic factor (
ANF) expression in the
E-domain peptide treated hearts. Taken together our data suggest that administration of the MGF
E-domain peptide derived from the propeptide form of IGF-1Ec may be used to facilitate the actions of
IGF-I produced by the tissue during the progression of
heart failure to improve cardiovascular function.