Hai-Zhen Ni1,2, Zhao Liu3, Li-Li Sun1, Min Zhou3, Chen Liu3, Wen-Dong Li3, Xiao-Qiang Li1,3. 1. Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, 215000, Jiangsu, China. 2. Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, 325000, Zhejiang, China. 3. Department of Vascular Surgery, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 218000, Jiangsu, China.
Abstract
Aim: To explore the underlying mechanisms of metformin on the angiogenic capacity of endothelial progenitor cells (EPCs). Results: EPC growth and miR-221 expression decreased concentration-dependence with metformin, and a negative correlation was observed between miR-221 expression and metformin concentration (p < 0.001). miR-221 overexpression using a mimic decreased the metformin-mediated angiogenic effects in EPCs (p < 0.01). Metformin increased p27 and LC3II expression and AMP-activated protein kinase (AMPK) phosphorylation, and decreased p62 expression, while miR-221 overexpression reversed the effects of metformin. Additionally, AMPK inhibition by compound C reversed the increase in p27 and LC3II levels and AMPK phosphorylation or miR-221 siRNA treatment. Conclusion: Metformin inhibits the angiogenic capacity of EPCs. The underlying mechanism involves AMPK-mediated autophagy pathway activity and increases miR-221-mediated p27 expression.
Aim: To explore the underlying mechanisms of metformin on the angiogenic capacity of endothelial progenitor cells (EPCs). Results: EPC growth and miR-221 expression decreased concentration-dependence with metformin, and a negative correlation was observed between miR-221 expression and metformin concentration (p < 0.001). miR-221 overexpression using a mimic decreased the metformin-mediated angiogenic effects in EPCs (p < 0.01). Metformin increased p27 and LC3II expression and AMP-activated protein kinase (AMPK) phosphorylation, and decreased p62 expression, while miR-221 overexpression reversed the effects of metformin. Additionally, AMPK inhibition by compound C reversed the increase in p27 and LC3II levels and AMPK phosphorylation or miR-221 siRNA treatment. Conclusion:Metformin inhibits the angiogenic capacity of EPCs. The underlying mechanism involves AMPK-mediated autophagy pathway activity and increases miR-221-mediated p27 expression.