In conclusion, for the first time, we showed that DBZ robustly protects against cardiac hypertrophy in rats after TAC surgery and in cardiomyocytes treated with Ang II, which is mostly due to the antioxidant and anti-ER stress properties of DBZ, via the mTOR/GSK3β(Ser9)/β-TrcP/NRF2 pathway. Here, ZNF365 is linked to cardiac hypertrophy.