APE1/ref1 gene provides anti-oxidative fate to Sca-1 positive cardiac progenitor cells and promotes cardiac repair via macrophage transition in ischemic environment

与DsRed-CPC相比，APE1-CPC在过氧化氢刺激下的ROS生成和细胞凋亡显著减少。在4周时，注射APE1-CPC的小鼠的LVEF的绝对变化显著大于安慰剂组，这与缩小梗塞范围有关。与DsRed-CPCs注射小鼠相比，注射APE1-CPCs的小鼠的移植细胞数显著增加。与DsRed-CPC注射组相比，APE1-CPC注射组小鼠梗死心肌中M1巨噬细胞数显著减少，而M2巨噬细胞数无明显减少。APE1/ref1基因可提高移植Sca1-CPC的存活能力，同时具有抗氧化应激作用。大量存活的Sca1-CPC修复了左心功能的丧失，这与减少梗死心肌和通过巨噬细胞转化的炎症有关。这些结果可能为APE1/ref1基因作为创新心肌细胞治疗的新靶点提供依据。

The ROS production and apoptosis stimulated by H2O2 were significantly reduced in Ape1-CPCs compared with DsRed-CPCs. At 4 weeks, the absolute change in the LVEF was significantly greater in Ape1-CPCs injected mouse, but not DsRed-CPCs, than in the placebo group, that was associated with reduced infarcted size. Ape1-CPCs injected mouse were significantly enhanced the engraft cells compared with DsRed-CPCs injected mouse. In infarct myocardium of Ape1-CPCs injected mouse, M1 macrophages, but not M2 macrophages, were significantly reduced compared with that of DsRed-CPCs injected mouse. APE1/ref1 gene enhances the survival of engraft Sca1-CPC accompanied with the redox effect against oxidative stress in ischemic myocardium. Great survived Sca1-CPCs repaired the loss of LV function, which were associated with reduced infarcted myocardium and inflammation via macrophage transition. These results may provide an APE1/ref1 gene as a novel target to innovate the cardiac cell-therapy.