Fig. 6

Working model of the mechanism by which Met alleviated AVP-induced cardiomyocyte hypertrophy through the AKT1–SERCA2 cascade. SERCA2 pumps Ca²⁺ into the sarcoplasmic reticulum and maintains the dynamic equilibrium of intracellular Ca²⁺. (left) In response to AVP induction, AKT1 is downregulated, and its inhibition of PLN and upregulation of SERCA2 are both attenuated. Moreover, the upregulation of PLN further inhibits Ca²⁺ transport through SERCA2. The intracellular Ca²⁺ concentration continues to rise and eventually leads to cardiomyocyte hypertrophy. (right) In H9C2 cells with AVP-induced hypertrophy, the inhibitory effect of AVP on AKT1 is attenuated by metoprolol. AKT1 inhibits PLN and upregulates SERCA2, and the excessive Ca²⁺ in the cytosol is pumped into the sarcoplasmic reticulum. Ultimately, the cardiomyocyte hypertrophy is alleviated