miR-376b-5p regulates angiogenesis in cerebral ischemia.

ABSTRACT

The profile of microRNAs (miRNAs) altered following middle cerebral artery occlusion (MCAO) and miRNAs are involved in angiogenesis following cerebral ischemia. miR­376b­5p was decreased following MCAO, however, whether miR­376b­5p is important in angiogenesis remains to be elucidated. The present study was designed to identify whether miR­376b­5p is involved in angiogenesis following cerebral ischemia and to elucidate the underlying mechanisms. A rat MCAO model was established and quantitative polymerase chain reaction was performed to analyze the mRNA expression level of miR­376b­5p for 1 to 7 days. In addition, the density of microvessels and the relative mRNA and protein levels of hypoxia­inducible factor­1 α (HIF­1α), vascular endothelial growth factor A (VEGFA) and Notch1 were measured. The miR­376b­5p mimic or the miR­376b­5p inhibitor were transfected into hypoxic human umbilical vein endothelial cells (HUVECs), and the proliferation, migration and tube formation were measured. To further examine the underlying mechanisms, shRNA was transfected into cells to knock down HIF­1α, and angiogenesis and the expression of associated molecules, including HIF­1α, VEGFA and Notch1 were compared between each group. Our results demonstrated that miR­376b­5p repressed angiogenesis in vivo and in vitro, and miR­376b­5p inhibited angiogenesis in HUVECs by targeting the HIF­1α­mediated VEGFA/Notch1 signaling pathway. These findings provide new insights into angiogenesis therapy for cerebral ischemia.