Hypoxia-induced SOCS3 is limiting STAT3 phosphorylation and NF-κB activation in congenital heart disease

► In chronic hypoxia cardiac myocytes. IL-6-STAT3 and NF-κB signaling pathways are sustained and stably activated to facilitate cells to adapt to hypoxia. ► Positive transactivation loop between p-STAT3 and NF-κB occurs. ► Expression of SOCS3 is induced by hypoxia, and suppresses STAT3 phosphorylation and mediates NF-κB activation. ► Overexpression of SOCS3 counteracts the cytoprotective effect of NF-κB and p-STAT3.