The role of serum exosomal miR-23a-3p and miR-375-3p in acute ischemic stroke

Objectives：Serum exosomal miRNAs are promising biomarkers and therapeutic targets for multiple diseases, but their expression profiles and functions in acute ischemic stroke (AIS) remain unclear. This study aimed to clarify the expression characteristics of serum exosomal miRNAs in AIS and explore the regulatory roles of key miRNAs in AIS progression.Methods：We first detected serum exosomal miRNA expression profiles of AIS patients and healthy controls via RNA-seq, then validated candidate miRNA levels using qRT-PCR. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of antithrombotic proteins [thrombomodulin (TM), endothelial NO synthase (eNOS), tissue plasminogen activator (t-PA)]. The regulatory effects of differentially expressed miRNAs on these proteins were verified in human umbilical vein endothelial cells (HUVEC) via transfection assays. Statistical analyses were performed using SPSS 26 and GraphPad Prism 8.Results：Compared with healthy controls, AIS patients exhibited significantly decreased serum exosomal levels of miR-23a-3p, miR-375-3p, and miR-122-5p, along with elevated serum TM, eNOS, and t-PA levels. miR-23a-3p and miR-375-3p could modulate the expression of TM, eNOS, and t-PA in HUVEC, and this regulatory relationship may be direct or indirect. The combination of these miRNAs and proteins achieved moderate predictive efficacy for AIS occurrence.Discussion：This study identifies serum exosomal miR-23a-3p and miR-375-3p as potential biomarkers for AIS and reveals their regulatory role in antithrombotic protein expression, providing novel insights into AIS's molecular mechanism and diagnostic strategies.