Effect of miR-150 targeting vascular endothelial growth factor on neurological rehabilitation and angiogenesis after cerebral infarction

Abstract:

Objective：To investigate whether miR-150 promotes angiogenesis in cerebral ischemic rats and to identify its possible mechanisms. Methods：SD rats were divided into four groups（n=15）：Sham group，MCAO（middle cerebral artery occlusion） group，MCAO+miR-150 group and MCAO+miR-NC group. Except for the Sham group，the other groups established MCAO models by electrocoagulation method. MCAO+miR-NC group and MCAO+miR-150 group were injected with PEG liposome embedded miR-NC or miR-150（2.4 mg/kg，iv），respectively. On the 14th day after modeling，the changes of neurological function，nerve damage and angiogenesis of MCAO rats were observed. The oxygen-glucose deprivation（OGD） brain microvascular endothelial cells（BMECs） models were established to determine the roles and possible mechanisms of miR-150 in angiogenesis. The binding site between miR-150 and vascular endothelial growth factor（VEGF） was verified by luciferase activity assay. Results：In vivo，miR-150 was signifi－cantly down-regulated in MCAO rats compared with the Sham group（1.00±0.03 vs. 0.34±0.04，P<0.05）. Up-regulation of miR-150 reduced neurological deficit scores（day 7：6.9±1.0 vs. 5.3±0.6，day 14：6.4±0.7 vs. 3.9±0.5，both P<0.01） and infarct volume[（13.8±1.6）% vs. （5.1±0.6）%，P<0.001]，and promoted angiogenesis in cerebral ischemic rats. Luciferase reporter gene analysis confirmed that VEGF gene was the target gene of miR-150，and the up-regulation of VEGF expression was observed in MCAO rats treated with miR-150. In vitro，up-regulation of miR-150 increased the co-expression of VEGF/VEGFR2 in OGD induced BMECs and promoted the tube formation. Mechanism analysis showed that the effect of miR-150 on promoting angiogenesis was related to the activation of VEGF pathway，and the activating effects of miR-150 were inhibited by SU1498. Conclusion：miR-150 regulates neurologic impairment and angiogenesis in MCAO rats by targeting VEGF.