2-aminoethoxydiphenylborane intervenes intracellular calcium signaling and attenuates myocardial ischemia-reperfusion injury in mice through ITPR1/MCU pathway.

Myocardial ischemia-reperfusion (MI/R) injury frequently occurs during the clinical management of ischemic heart disease. The underlying mechanism includes neutrophil infiltration, heightened intracellular Ca levels, mitochondrial energy metabolism disorder. This study investigated the pathological role of the inositol 1,4,5-trisphosphate receptor/mitochondrial calcium uniporter (ITPR1/MCU) pathway in regulating disturbances in intracellular calcium ([Ca]) and mitochondrial calcium ([Ca]) levels during MI/R injury. Furthermore, the study explored the potential of 2-aminoethoxydiphenylborane (2-APB) as a cardioprotective agent against MI/R injury. The outcomes of this investigation demonstrated that the ITPR1/MCU pathway was activated after MI/R, leading to [Ca]/[Ca] overload, impairing mitochondrial structure and function, and promoting cardiomyocyte death. The administered treatment attenuates myocardial injury after MI/R by reversing the [Ca]/[Ca] imbalance, maintaining cardiomyocyte mitochondrial homeostasis and promoting cardiomyocyte survival. Furthermore, the administration of 2-APB exerted a suppressive effect on MCU expression. Notably, the activation of MCU abolished the cardioprotective impact mediated by 2-APB. These results suggest that 2-APB intervenes [Ca]/[Ca] balance and maintains mitochondrial function through the ITPR1/MCU pathway. The strategic manipulation of this pathway holds promise as a prospective avenue for the clinical treatment of MI/R injury.