DNA Damage Response Mediates Pressure Overload-Induced Cardiomyocyte Hypertrophy

The study demonstrated that pressure overload induced DNA double-strand breaks (DSBs) in cardiomyocytes, leading to the activation of the ATM kinase, a key component of the DNA damage response (DDR). The research used angiotensin II-infused and transverse aortic constriction (TAC) mouse models to show that ATM activation was associated with cardiomyocyte hypertrophy. Inhibition of ATM, either pharmacologically with KU60019 or through genetic deletion, significantly reduced hypertrophy, indicating that ATM plays a crucial role in this process. The study also found that ATM influences hypertrophy by modulating calcineurin and 4E-BP1 pathways. These findings suggested that targeting DDR, specifically ATM, could be a potential therapeutic strategy for managing pressure overload-induced cardiac hypertrophy.