AGGF1-primed endothelial progenitor cells alleviate ischaemia-reperfusion injury in diabetic hearts.

A number of cardioprotective pharmacological agents are not effective in diabetic hearts. The role of AGGF1-EPCs therapy in diabetic ischaemia-reperfusion(I/R) injury and the underlying mechanism by which AGGF1 regulates EPCs under hyperglycemia (HG) + hypoxia/reoxygenation (H/R) stress are still unclear. We observed that the damaging effects of HG + H/R on EPCs were abolished by AGGF1. The EPCs implantation therapy successfully restores cardiac functions, inhibits ROS production and fibrosis in diabetic I/R mice. Mechanistically, AGGF1 activates the Nrf2 and induces the activation of downstream antioxidative proteins (HO1, NQO1, and CAT). These data suggest that AGGF1 protein reverses the damaging effects of HG + H/R on EPCs via the antioxidative Nrf2. AGGF1-EPCs therapy is a novel strategy for treating diabetic I/R injury.