Mir-130a potentiates the reparative properties of human endothelial colony forming cells facing hypoxia via VEGFR2 and STAT3

Hypoxia controls reparative angiogenesis. MiRNAs are master regulators of gene expression in hypoxia and angiogenesis. However, we do not yet have a clear understanding of how hypoxia-induced miRNAs modulate vasoreparative processes. Here, we identify miR-130a as a mediator of the hypoxic response in human primary endothelial colony forming cells (ECFCs), a well-characterized subtype of endothelial progenitor. Under hypoxic conditions, miR-130a overexpression enhances ECFC pro-angiogenic capacity in vitro and potentiates their vasoreparative properties in vivo. Mechanistically, miR-130a orchestrates upregulation of VEGFR2, activation of STAT3-dependent transcription, and accumulation of HIF1a via translational inhibition of DDX6. These findings unveil a new role for miR-130a in hypoxia, whereby it modulates the VEGFR2/STAT3/HIF1a axis to increase the vasoregenerative capacity of ECFCs. Overall design: hypoxia response in ECFCs