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

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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).

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Most cited references 27

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Moyamoya disease: current concepts and future perspectives.

Satoshi Kuroda, Kiyohiro Houkin (2008)

Moyamoya disease is an uncommon cerebrovascular disease that is characterised by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. The disease is associated with the development of dilated, fragile collateral vessels at the base of the brain, which are termed moyamoya vessels. The incidence of moyamoya disease is high in east Asia, and familial forms account for about 15% of patients with this disease. Moyamoya disease has several unique clinical features, which include two peaks of age distribution at 5 years and at about 40 years. Most paediatric patients have ischaemic attacks, whereas adult patients can have ischaemic attacks, intracranial bleeding, or both. Extracranial-intracranial arterial bypass, including anastomosis of the superficial temporal artery to the middle cerebral artery and indirect bypass, can help prevent further ischaemic attacks, although the beneficial effect on haemorrhagic stroke is still not clear. In this Review, we summarise the epidemiology, aetiology, clinical features, diagnosis, surgical treatment, and outcomes of moyamoya disease. Recent updates and future perspectives for moyamoya disease will also be discussed.

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The role of miR-126 in embryonic angiogenesis, adult vascular homeostasis, and vascular repair and its alterations in atherosclerotic disease.

Dimitry A. Chistiakov, Alexander N. Orekhov, Yuri V. Bobryshev (2016)

Expression of microRNA (miR)-126 is enriched in endothelial cells (ECs) and endothelial progenitor cells (EPCs). MiR-126 is considered a master regulator of physiological angiogenesis. In embryonic vasculogenesis, this miRNA is involved in induction of angiogenic signaling, supports differentiation of embryonic stem cells to EPCs and ECs, and promotes EC maturation. However, in mature ECs and adult EPCs, miR-126 contributes to vascular homeostasis by inhibiting angiogenesis and maintaining the quiescent endothelial phenotype associated with increased vascular integrity and inhibited proliferation and motility. In a case of vessel injury and/or hypoxia, miR-126 up-regulation activates EPCs and ECs and contributes to vascular healing and neovessel formation. Indeed, miR-126 exhibits vasculoprotective and atheroprotective properties. The promising regenerative and proangiogenic potential of this miRNA will be helpful for development of cardioprotective strategies and cardiovascular repair therapies of myocardial infarction, heart failure, and other cardiovascular pathology.

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Surgical treatment of moyamoya disease in pediatric patients--comparison between the results of indirect and direct revascularization procedures.

K. Hasuo, T Matsushima, M Fukui … (1992)

Either encephaloduroarteriosynangiosis (EDAS) or superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis combined with encephalomyosynangiosis (EMS) has been performed on most of the children with moyamoya disease in our department. EDAS alone was done in the parietal region of 13 sides in 10 patients, and STA-MCA anastomosis with EMS in the parietal region was done on 7 sides in 6 patients. The surgical results of these two different procedures were then compared. Postoperative collateral formation was observed on external carotid angiograms, and the improvement of clinical symptoms was monitored for 1 year after the bypass procedure. STA-MCA anastomosis with EMS was found to be superior to EDAS in both the development of collateral circulation (P less than 0.05) and postoperative clinical improvement (P less than 0.01). EDAS can be done easily and safely on small children with moyamoya disease, but STA-MCA anastomosis with EMS is considered to be more appropriate, whenever possible.

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Author and article information

Journal

Journal ID (nlm-ta): Aging (Albany NY)

Journal ID (iso-abbrev): Aging (Albany NY)

Journal ID (publisher-id): Aging

Title: Aging (Albany NY)

Publisher: Impact Journals

ISSN (Electronic): 1945-4589

Publication date Collection: 15 July 2020

Publication date (Electronic): 09 July 2020

Volume: 12

Issue: 13

Pages: 13234-13254

Affiliations

[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

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[*]

Equal contribution

Correspondence to: Chuan Chen; email: dr_oliver_chen@163.com

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Publisher ID: 103431 Publisher ID: 103431

DOI: 10.18632/aging.103431

PMC ID: 7377842

PubMed ID: 32644942

SO-VID: 529ebdb7-6d1d-47f6-acaf-bd0118f54d55

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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.

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

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Most cited references 27

Moyamoya disease: current concepts and future perspectives.

The role of miR-126 in embryonic angiogenesis, adult vascular homeostasis, and vascular repair and its alterations in atherosclerotic disease.

Surgical treatment of moyamoya disease in pediatric patients--comparison between the results of indirect and direct revascularization procedures.

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