The PI3K/AKT pathway is upstream of NF-κB, and AKT activation prompts the translocation of NF-κB to the nucleus, where it acts as an inflammatory factor in cardiac tissue.35,36 Inhibiting the AKT/NF-κB pathway mitigates ISO-induced cardiac remodelling.37 Additionally, recent studies have shown that blocking the NF-κB pathway can reduce the susceptibility to VAs following HF.24,38 In our study, the PI3K/Akt/NF-κB signalling pathway is identified as responsible for the protective effects of TNIP3 overexpression in ISO-induced HF. This evidence concerns the gene AKT1 and hydrops fetalis.