Serum Exosomal mir-340-5p Promotes Angiogenesis in Brain Microvascular Endothelial Cells During Oxygen-Glucose Deprivation

摘要

Ischemic stroke (IS) is a cerebrovascular disease with high morbidity, recurrence, and mortality. The purpose of the present study was to investigate the role and mechanism of human serum exosomes on angiogenesis after IS. The middle cerebral artery occlusion (MCAO) in vivo model and oxygen-glucose deprivation (OGD) in vitro model were established. Human serum exosomes from healthy samples (NC-exo) and IS samples (IS-exo) were injected into MCAO mice. Neurobehavioral tests were performed to assess the extent of neurological deficits. The infarct volume was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA). In addition, human serum exosomes were cocultured with brain microvascular endothelial cells (BMECs). Cell Counting Kit-8 (CCK-8), Transwell, and tubule formation assays were performed to investigate the proliferation, migration, invasion, length, and branching of BMECs. The miRNA expression profiles of NC-exo and IS-exo were analyzed by high-throughput sequencing and compared. Bioinformatics and luciferase reporter assays were performed to evaluate the relationship between miR-340-5p and CD147. Serum NC-exo and IS-exo had protective effects on IS injury and promoted BMEC angiogenesis. Interestingly, the protective effect of IS-exo was weaker than that of NC-exo. In addition, miR-340-5p was downregulated in IS-exo, and miR-340-5p accelerated angiogenesis of BMECs after OGD. Mechanistically, CD147 was confirmed as a direct target of miR-340-5p. Finally, miR-340-5p promoted angiogenesis by directly targeting CD147. Serum exosome-derived miR-340-5p promote angiogenesis in OGD-induced BMECs by targeting CD147.