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14.04.2020 | Original Article

Implication of MicroRNA503 in Brain Endothelial Cell Function and Ischemic Stroke

verfasst von: Huiting Zhang, Qunwen Pan, Zi Xie, Yanyu Chen, Jinju Wang, Ji Bihl, Wangtao Zhong, Yanfang Chen, Bin Zhao, Xiaotang Ma

Erschienen in: Translational Stroke Research | Ausgabe 5/2020

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Abstract

The role of miR-503 in brain endothelium and ischemic stroke (IS) remains unclear. We aimed to study the relationship between plasma miR-503 and the onset time, severity, subtypes, and von Willebrand Factor (vWF) level in IS patients and to investigate the roles and underlying mechanisms of miR-503 in middle cerebral artery occlusion (MCAO) mice and cultured cerebral vascular endothelial cells (ECs). In MCAO mice, the effects of plasma from acute severe IS patients (ASS) with or without miR-503 antagomir on brain and ECs damage were determined. In cultured human ECs, the effects of miR-503 overexpression or knockdown on the monolayer permeability, apoptosis, ROS, and NO generation were investigated. For mechanism study, the PI3K/Akt/eNOS pathway, cleaved caspase-3, and bcl-2 were analyzed. Results showed that plasma miR-503 was significantly increased in IS patients, especially in acute period and severe cases and subtypes of LAA and TACI, and was positively correlated with vWF. Logistic analysis indicated that miR-503 was an independent risk factor for IS, with the area under curve of 0.796 in ROC analysis. In MCAO mice, ASS pretreatment aggravated neurological injury, BBB damage, brain edema, CBF reduction, and decreased NO production while increased apoptosis and ROS generation in brain ECs, which were partly abolished by miR-503 antagomir. In cultured ECs, miR-503 overexpression and knockdown confirmed its effects on regulating monolayer permeability, cell apoptosis, NO, and ROS generation via PI3K/Akt/eNOS pathway or bcl-2 and cleaved caspase-3 proteins. These together indicate that miR-503 is a promising biomarker and novel therapeutic target for IS.

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Titel: Implication of MicroRNA503 in Brain Endothelial Cell Function and Ischemic Stroke
verfasst von: Huiting Zhang
Qunwen Pan
Zi Xie
Yanyu Chen
Jinju Wang
Ji Bihl
Wangtao Zhong
Yanfang Chen
Bin Zhao
Xiaotang Ma
Publikationsdatum: 14.04.2020
Verlag: Springer US
Erschienen in: Translational Stroke Research / Ausgabe 5/2020
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-020-00794-0

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Implication of MicroRNA503 in Brain Endothelial Cell Function and Ischemic Stroke

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