FTO alleviated ferroptosis in septic cardiomyopathy via mediating the m6A modification of BACH1.

Sepsis is a global health challenge that results in systemic inflammation, oxidative stress, and multi-organ dysfunction, with the heart being particularly susceptible. This study aimed to elucidate the effect of FTO, a key regulator in mA methylation in septic cardiomyopathy, and its potential therapeutic implications. Cellular and animal models of septic myocardial injury were established. Moreover, it was revealed that ferroptosis, which is a form of programmed necrosis occurring with iron dependence, was activated within cardiomyocytes during septic conditions. The overexpression of FTO-suppressed ferroptosis alleviated heart inflammation and dysfunction and improved survival rates in vivo. However, the protective effects of FTO were attenuated by the overexpression of BACH1, which is a molecule negatively correlated with FTO. Mechanistically, FTO modulated the mA modification of BACH1, suggesting a complex interplay in the regulation of cardiomyocyte damage and sepsis. Our findings reveal the potential of targeting the FTO/BACH1 axis and ferroptosis inhibitors as therapeutic strategies for sepsis-induced cardiac injuries.