miRNA Profiling of Circulating Small Extracellular Vesicles From Subarachnoid Hemorrhage Rats Using Next-Generation Sequencing

Abstract

Background: Extracellular vesicles (EVs) are produced during abnormal and normal physiological conditions. Understanding the expression profile of microRNA (miRNA) in plasma-derived small extracellular vesicles (sEVs) and their roles in subarachnoid hemorrhage (SAH) that cause cerebral vasospasm (CVS) is imperative. Methods: Sprague Dawley rats (250–300 g) were allocated to sham or SAH groups established using endovascular perforation method. miRNA expression profiles of plasma sEVs in both groups (each n = 4) were evaluated using next-generation sequencing (NGS). Results: There were 142 microRNAs (miRNAs) significantly expressed differently between the two groups, of which 73 were up-regulated while 69 were down-regulated in SAH sEVs compared with those of sham (p < 0.05; fold change ≥ 2). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses of differently expressed (DE) miRNAs revealed signaling pathways and target genes (TGs) in the SAH group. rno-miR-185-5p, rno-miR-103-3p, rno-miR-15b-3p, rno-miR-93-5p, and rno-miR-98-5p were the top five most up-regulated sEVs miRNAs. Conclusion: Our results suggest that miRNA can be selectively packaged into sEVs under SAH, and this could help develop potential targets for the prevention, diagnosis, and treatment of CVS after this condition.