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

Abstract 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...

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Main Authors: Xia Li, Suwan Mu, Shuting Huang, Congcong Dai, Yumei Li, Jianqiao Li, Liang Zhong, Miaoling Wei, Liuqing Wei, Yong Li
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-06190-8
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Summary:Abstract 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.
ISSN:2045-2322