Serum Mir-369-3p Downregulation Correlates with Poor Prognosis in Acute Ischemic Stroke and Mitigates Endothelial Injury by Targeting VAV3

Globally, acute ischemic stroke (AIS) continues to be a major contributor to death and long-term functional impairment. The present work investigates the clinical relevance of miR-369-3p in AIS and how it regulates brain microvascular endothelial cells. Quantitative measurements of serum miR-369-3p were conducted in a cohort comprising 138 individuals with AIS and 120 healthy controls. ROC curve analysis and Cox proportional hazards regression were employed to evaluate diagnostic and prognostic performance of miR-369-3p. Human brain microvascular endothelial cells (hCMEC/D3) were exposed to oxygen-glucose deprivation followed by reoxygenation (OGD/R), allowing assessment of how miR-369-3p influences cell viability, inflammatory responses, and the expression of adhesion molecules. Downstream target genes were identified through bioinformatics analysis and validated using a dual-luciferase assay. A statistically significant reduction in serum miR-369-3p levels was observed among AIS patients relative to controls (P < 0.001), and this miRNA demonstrated favorable diagnostic accuracy. Lower expression of miR-369-3p emerged as an independent predictor of poorer functional outcomes, as assessed by the modified Rankin Scale (mRS) score at 90 days post‑stroke. In cellular studies, upregulation of miR-369-3p mitigated the loss of cell viability induced by OGD/R, reduced the production of pro‑inflammatory cytokines and lowered the levels of ICAM‑1 and VCAM‑1. Furthermore, VAV3 was confirmed as a direct target of miR-369-3p; restoring VAV3 expression counteracted the protective effects conferred by miR-369-3p. Serum miR-369-3p may serve as a non-invasive diagnostic and prognostic biomarker for AIS. Mechanistically, miR-369-3p protects against ischemic endothelial injury by targeting VAV3 and mitigating inflammation and adhesion molecule expression.