Hepatocyte growth factor (HGF) and insulin-like growth factor 1 (IGF-1) improved ventricular remodeling after myocardial infarction through inhibiting MMP8/13 in a rat model

Background: Hepatocyte growth factor (HGF) and insulin-like growth factor 1 (IGF-1) have been reported on promoting the recovery after myocardial infarction (MI). We try to investigate the effect of HGF and IGF-1 on ventricular remodeling (VR) after MI and figure out how it works.Methods: Forty-eight male SD rats were randomized to receive PBS, HGF, IGF-1 and GFs (a mix of HGF and IGF-1) by intramyocardial injection 2 weeks after MI. Echocardiography was performed before and 6 weeks after the injection. Then, histopathological examination performed. The mRNA and protein expression of matrix metalloproteinases 8/13 (MMP8/13), p38 MAPK and PI3K/Akt were measured.Results: HGF, IGF-1 and GFs group indicated improving cardiac structure and function with dLVIDd, dLVIDs, dIVS and dLVPW decreased while dLVEF and dLVFS increased compared with those in PBS group (P<0.05, respectively). And HE staining showed that the myocardial cells in HGF, IGF-1 and GFs group arranged more regularly compared with PBS group. Masson staining showed that the area of myocardial fibrosis in PBS group expanded compared with HGF, IGF-1 and GFs group. The mRNA and protein expression of MMP8/13 in HGF, IGF-1 and GFs group were lower than PBS group (P<0.05, respectively). Further study showed that mRNA and protein expression of p38 MAPK in GFs and HGF group were higher than PBS group (P<0.05, respectively), while no significant difference was seen between them (P>0.05, respectively). Similarly, mRNA and protein expression of PI3K/Akt in GFs and IGF-1 group increased compared with PBS group (P<0.05, respectively). But there was no significant difference between them (P>0.05, respectively).Conclusions: HGF and IGF-1 improved VR after MI by suppressing MMP 8/13, which may through p38 MAPK and PI3K/Akt pathway respectively.