AKT1 and heart failure: Based on the above observations, we formulated following working model (Fig. 10): Pressure overload (TAC) activates MAPK and AKT/GSK3β, and subsequently promotes GATA4 trans-location from cytoplasm to nucleus, activates HF genes, and finally leads to HF; XML inhibits the phosphorylation of ERK1/2, and AKT/GSK3β pathway, which subsequently decreases the expression of transcription factor GATA4, resulting in inhibition of heart failure.