Graphic summary of endothelial miR-15a/16-1 in the regulation of post-stroke angiogenesis. In the stroke brain, endothelium-targeted deletion of the miR-15a/16-1 cluster (EC-miR-15a/16-1 cKO) abolishes the brain endothelial miR-15a/16-1 expression, allowing release from its translational repression of downstream key pro-angiogenic factors. This release results in the upregulation of VEGFA, FGF2 and their receptors VEGFR2 and FGFR1. The enhanced VEGF-VEGFR2, and FGF2-FGFR1 signaling cascades trigger the phosphorylation of Src and its downstream mediators, such as Akt, Stat3, p38 MAPK, p44/42 MAPK, and FAK, and promote endothelial proliferation and angiogenesis. AZD0530, a specific pharmacological inhibitor of Src, blocks the Src phosphorylation and the downstream signaling pathway, obstructing the improvement in angiogenesis in the ischemic brains of EC-miR-15a/16-1 cKO mice. VEGFA: vascular endothelial growth factor; FGF2: fibroblast growth factor 2; VEGFR2: vascular endothelial growth factor receptor 2; FGFR1: fibroblast growth factor receptor 1; Akt: protein kinase B; Stat3: signal transducer and activator of transcription 3; MAPK: mitogen-activated protein kinase; FAK: focal adhesion kinase.