IGF-1 Expression in Infarcted Myocardium and MGF E Peptide Actions in Rat Cardiomyocytes in Vitro

Abstract

Insulinlike growth factor-1 (IGF-1) expression is implicated in myocardial pathophysiology, and two IGF-1 mRNA splice variants have been detected in rodents, IGF-1Ea and mechano-growth factor (MGF). We investigated the expression pattern of IGF-1 gene transcripts in rat myocardium from 1 h up to 8 wks after myocardial infarction induced by left anterior descending coronary artery ligation. In addition, we characterized IGF-1 and MGF E peptide action and their respective signaling in H9C2 myocardial-like cells in vitro. IGF-1Ea and MGF expression were significantly increased, both at transcriptional and translational levels, during the late postinfarction period (4 and 8 wks) in infarcted rat myocardium. Measurements of serum IGF-1 levels in infarcted rats were initially decreased (24 h up to 1 wk) but remained unaltered throughout the late experimental phase (4 to 8 wks) compared with sham-operated rats. Furthermore, specific anti-IGF-1R neutralizing antibody failed to block the synthetic MGF E peptide action, whereas it completely blocked IGF-1 action on the proliferation of H9C2 cells. Moreover, this synthetic MGF E peptide did not activate Akt phosphorylation, whereas it activated ERK1/2 in H9C2 rat myocardial cells. These data support the role of IGF-1 expression in the myocardial repair process and suggest that synthetic MGF E peptide actions may be mediated via an IGF-1R independent pathway in rat myocardial cells, as suggested by our in vitro experiments.