Study of the mechanism of action of 4-octyl itaconate in attenuating myocardial ischemia-reperfusion injury after heart transplantation

It is important to mitigate myocardial ischemia-reperfusion (IR) injury for improving the success of heart transplantation (HT) and the quality of life of patients.4-OI is a derivative of itaconate with similar chemical properties and biological activities as itaconate. However, 4-OI could overcome the limitations of itaconate in in vivo applications such as inefficient cellular uptake and rapid metabolism, making it more suitable for exploratory studies in the therapeutic direction.In our study, we demonstrated that 4-OI is an effective therapeutic strategy against myocardial ischemia-reperfusion injury after heart transplantation. Overall design: We established a syngeneic cervical heterotopic heart transplantation model in recipient mice undergoing cardiac transplantation with or without intraperitoneal injection of 4-OI (50 mg/kg) 12 h before and 2 h after reperfusion, and the recipient mice were then executed 24 h after reperfusion to remove the transplanted hearts.