Implication of MicroRNA503 in Brain Endothelial Cell Function and Ischemic Stroke

Area of Science:

• Neuroscience
• Molecular Biology
• Cardiovascular Research

Background:

• The role of microRNA-503 (miR-503) in the brain endothelium and its involvement in ischemic stroke (IS) are not well understood.
• Investigating miR-503's relationship with IS onset, severity, subtypes, and associated biomarkers like von Willebrand Factor (vWF) is crucial.

Purpose of the Study:

• To examine the association between plasma miR-503 levels and clinical characteristics of IS patients.
• To elucidate the functional role and molecular mechanisms of miR-503 in cerebral endothelial cells using mouse models and in vitro studies.

Main Methods:

• Analysis of plasma miR-503 levels in IS patients, correlating with clinical data and vWF.
• Utilizing middle cerebral artery occlusion (MCAO) mouse models and cultured human cerebral vascular endothelial cells (ECs).
• Investigating the effects of miR-503 manipulation (overexpression/knockdown, antagomir treatment) on ECs' barrier function, apoptosis, ROS, and NO production, and analyzing key signaling pathways (PI3K/Akt/eNOS) and apoptosis markers (cleaved caspase-3, bcl-2).

Main Results:

• Plasma miR-503 levels were significantly elevated in IS patients, particularly in acute and severe cases, and correlated positively with vWF.
• miR-503 was identified as an independent risk factor for IS, with strong diagnostic potential (AUC=0.796).
• In MCAO mice and cultured ECs, miR-503 modulated endothelial barrier integrity, apoptosis, ROS, and NO production, primarily through the PI3K/Akt/eNOS pathway and apoptosis-related proteins.

Conclusions:

• miR-503 is a potential biomarker for ischemic stroke diagnosis and prognosis.
• miR-503 plays a significant role in the pathogenesis of ischemic stroke by affecting cerebral endothelial cell function.
• Targeting miR-503 presents a novel therapeutic strategy for ischemic stroke.