Conditioned Medium Reduces Isoproterenol-Induced Myocardial Damage Via MAPK/NF-κB Pathway

Abstract

The present work was conducted to examine the cardioprotective effects of conditioned medium (CM) obtained from human amniotic membrane mesenchymal stem cells (hAMSCs-CM) in a rat model of isoproterenol (ISO)-induced myocardial damage and to clarify its effect on activity of mitogen-activated protein kinase (MAPK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. ISO was subcutaneously injected at 170 mg/kg/day for 4 consecutive days to create model. The cardiac function was determined using echocardiography. The expression of inflammatory cytokine was investigated using enzyme-linked immunosorbent assay (ELISA). The activity of MAPK/NF-κB was evaluated by immunohistochemistry assay. Trichrome Masson’s staining was used to evaluate the fibrosis. ISO-induced myocardial damage was indicated by loss of cardiac function, excessive secretion of inflammatory cytokines, increased fibrosis and activity of NF-κB and increasing phosphorylated levels of p38 MAPK. Intramyocardial post-treatment with 150 µL of hAMSCs-CM significantly improved heart function and reduced fibrosis and expression levels of inflammatory cytokines, NF-κB expression, and phosphorylated levels of p38 MAPK (p < 0. 05). Collectively, findings of present study demonstrate that cardioprotective effects of hAMSCs-CM are associated with attenuation of inflammation through reduction in activity of MAPK/NF-κB pathway. This can be attributed to paracrine factors secreted by MSCs including exosomes, cytokines, antiapoptotic, angiogenic, and growth factors.