Sesn2 overexpression could mitigate pressure overload-induced cardiac hypertrophy in vivo and Ang II-induced NRCMs hypertrophy in vitro via activating AMPKα2, depressing ACC1/mTORC1 signaling, and oxidative stress, as well as restoring Nrf2/HO-1 signaling. Here, AGT is linked to cardiac hypertrophy.