Implication of MicroRNA503 in Brain Endothelial Cell Function and Ischemic Stroke.
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.
['Zhang|Huiting|H|', 'Pan|Qunwen|Q|', 'Xie|Zi|Z|', 'Chen|Yanyu|Y|', 'Wang|Jinju|J|', 'Bihl|Ji|J|', 'Zhong|Wangtao|W|', 'Chen|Yanfang|Y|', 'Zhao|Bin|B|', 'Ma|Xiaotang|X|0000-0002-0657-5556']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D001921:Brain D002545:Brain Ischemia D042783:Endothelial Cells D005260:Female D006801:Humans D000083242:Ischemic Stroke D008297:Male D035683:MicroRNAs D008875:Middle Aged D019869:Phosphatidylinositol 3-Kinases D055815:Young Adult
Endothelial cells Ischemic stroke MiR-503 Biomarker