Research Paper Volume 12, Issue 13 pp 13234—13254
Increasing the expression of microRNA-126-5p in the temporal muscle can promote angiogenesis in the chronically ischemic brains of rats subjected to two-vessel occlusion plus encephalo-myo-synangiosis
- 1 Department of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, PR China
- 2 Department of Rehabilitation, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, PR China
Received: January 6, 2020 Accepted: April 27, 2020 Published: July 9, 2020
https://doi.org/10.18632/aging.103431How to Cite
Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: miR-126-5p plays an important role in promoting endothelial cell (EC) proliferation. We thus explored whether miR-126-5p can promote EC proliferation and angiogenesis in chronically ischemic brains (CIBs).
Results: Improved revascularization in moyamoya patients was correlated with upregulated miR-126-5p expression in the TM and DM. In vitro experiments showed that miR-126-5p promoted EC proliferation through the PI3K/Akt pathway. CIBs from the agomir group exhibited significantly higher p-Akt, VEGF, CD31 and eNOS expression compared with the control CIBs. The ICBP and the RCF were significantly better in the agomir compared with the control group.
Conclusion: Increasing miR-126-5p expression in the TM can promote EC proliferation and angiogenesis in CIBs of 2VO+EMS rats through the PI3K/Akt pathway.
Methods: We assessed the correlation between revascularization and miR-126-5p expression in the temporal muscle (TM) and dura mater (DM) of moyamoya patients. The effect of miR-126-5p on EC proliferation and downstream signaling pathways was explored in vitro. We established an animal model of two-vessel occlusion plus encephalo-myo-synangiosis (2VO+EMS), transfected the TM with miR-126-5p agomir/antagomir, compared the expression of miR-126-5p and relevant downstream cytokines in brain tissue among different groups, and investigated the improvement in cerebral blood perfusion (ICBP) and the recovery of cognitive function (RCF).
Abbreviations
2VO: 2-vessel occlusion; ASL: arterial spin labeling; CBF: cerebral blood flow; CBP: cerebral blood perfusion; CCA: common carotid artery; CCI: chronic cerebral ischemia; DM: dura mater; DSA: digital subtraction angiography; ECs: endothelial cells; EC-IC: extracranial-to-intracranial; EMS: encephalo-myo-synangiosis; eNOS: endothelial nitric oxide synthase; HUVECs: human umbilical vein endothelial cells; MCA: middle cerebral artery; miRNA: microRNA; MWM: Morris water maze; NC: negative control; NS: normal saline; qRT-PCR: quantitative real-time polymerase chain reaction; ROI: region of interest; SEM: scanning electron microscopy; TM: temporal muscle; VEGF: vascular endothelial growth factor; vWF: von Willebrand factor.