Bone Marrow Mesenchymal Stem Cell-Derived Exosomal MiR-744-5p Alleviates Obstructive Sleep Apnea-Induced Myocardial Injury by Targeting NFIX

Abstract

Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapses during sleep, which leads to intermittent hypoxia, a risk factor of OSA-related cardiovascular morbidity.In this work, exosome isolation and identification with ultracentrifugation, transmission electron microscopy, nanoparticle tracking analysis, and Western blot assay were carried out. H9C2 cells were subjected to chronic intermittent hypoxia (CIH) treatment, which was followed by bone marrow mesenchymal stem cell (BMSC)-derived exosome treatment. Through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the expression of miR-744-5p was determined. Using corresponding commercial kits, the levels of oxidative stress indicators and inflammatory factors were measured. The potential target genes of miR-744-5p were predicted using four publicly target-predicting databases. To verify the interaction between miR-744-5p and NFIX, RNA pulldown and luciferase reporter assays were conducted.Significant upregulated expression of miR-744-5p in BMSC-derived exosomes was observed. The exosomes derived from miR-744-5p-overexpressing BMSCs (miR-744-5p mimics/Exo) promoted cell viability and reduced excessive inflammation and oxidative stress. Additionally, the intermolecular interaction between miR-744-5p and NFIX was determined. The exosomes derived from BMSCs cotransfecting with NFIX overexpression plasmid and miR-744-5p mimics reversed the miR-744-5p mimics/Exo-induced inhibitory effects on CIH-caused cardiomyocyte injury.BMSC-derived exosomal miR-744-5p suppressed OSA-induced cardiomyocyte damage by targeting NFIX.