Ferroptosis exacerbates myocardial ischemia-reperfusion injury via worsening oxidative stress and inflammatory responses: the role of Ferritin/SLC7A11/GPX-4 signaling pathway

Abstract Ferroptosis is closely linked to pathological processes in cardiomyocytes. However, the role of ferroptosis in myocardial ischemia-reperfusion injury (MI/RI) and its underlying mechanisms are unknown. Transitional accumulation of iron ions, as well as oxidative stress and lipid peroxidation production were found in the MI/RI model. These were significantly inhibited by an iron death inhibitor. In MI/RI-induced tissue damage and inflammatory responses, inhibition of ferroptosis reduced cardiac infarct area and resisted inflammation. Mechanistic investigations show that inhibition of ferroptosis via the Ferritin/SLC7A11/GPX-4 axis can target MI/RI mitigation, highlighting the potential of inhibiting ferroptosis as a novel strategy for therapeutic of MI/RI.