Effects of Atrial Fibrillation-Derived Exosome Delivery of miR-107 to Human Umbilical Vein Endothelial Cells.

Abstract

The aim of this study was to explore the effects of atrial fibrillation (AF)-derived exosome delivery of miR-107 to human umbilical vein endothelial cells (HUVECs) and its related mechanisms. Exosomes were isolated from the plasma of patients with AF and healthy controls, followed by characterization. The expression levels of miR-320d, miR-103a-3p, and miR-107 were measured using real-time quantitative PCR (RT-qPCR). The dual-luciferase reporter gene was used to verify the downstream target of miR-107. Afterward, HUVECs were treated with AF-derived exosomes or transfected with miR-107 mimics. After cell culture, Cell Counting Kit-8, Transwell, and flow cytometry were used to determine cell viability, migration, and apoptosis and cell cycle phase. Finally, RT-qPCR was performed to examine the expression of related genes. NanoSight, transmission electron microscopy, and western blotting showed that exosomes were successfully isolated, and that AF-derived exosomes could be taken up by HUVECs. The expression of miR-107 was significantly higher in AF-derived exosomes than in normal exosomes (p < 0.05). USP14 was shown to be the direct target of miR-107. In addition, miR-107 mimics and AF-derived exosomes significantly suppressed cell viability and migration (p < 0.05) and enhanced cell apoptosis; they also increased G0/G1-phase cells and reduced S-phase cells. RT-qPCR showed that exosomal miR-107 overexpression significantly downregulated the expression of USP14 and Bcl2 (p < 0.05), whereas it markedly upregulated the expression of ERK2, FAK, and Bax (p < 0.05). AF-derived exosomes can deliver miR-107 to HUVECs, and exosomal miR-107 may regulate cell viability, migration, and apoptosis and cell cycle progression by mediating the miR-107/USP14 pathway.