Loading MiR-210 in Endothelial Progenitor Cells Derived Exosomes Boosts Their Beneficial Effects on Hypoxia/Reoxygeneation-Injured Human Endothelial Cells via Protecting Mitochondrial Function

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Background/Aims: Stem cell-derived exosomes (EXs) offer protective effects on various cells via their carried microRNAs (miRs). Meanwhile, miR-210 has been shown to reduce mitochondrial reactive oxygen species (ROS) overproduction. In this study, we determined the potential effects of endothelial progenitor cell-derived EXs (EPC-EXs) on hypoxia/ reoxygenation (H/R) injured endothelial cells (ECs) and investigated whether these effects could be boosted by miR-210 loading. Methods: Human EPCs were used to generate EPC-EXs, or transfected with scrambler control or miR-210 mimics to generate EPC-EXssc and EPC-EXsmiR-210. H/R-injured human ECs were used as a model for functional analysis of EXs on apoptosis, viability, ROS production and angiogenic ability (migration and tube formation) by flow cytometry, MTT, dihydroethidium and angiogenesis assay kits, respectively. For mechanism analysis, the mitochondrion morphology, membrane potential (MMP), ATP level and the expression of fission/fusion proteins (dynamin-related protein 1: drp1 and mitofusin-2: mfn2) were assessed by using JC-1 staining, ELISA and western blot, respectively. Results: 1) Transfection of miR-210 mimics into EPCs induced increase of miR-210 in EPC-EXsmiR-210 without change of average size; 2) EPC-EXsmiR-210, but not EPC-EXs or EPC-EXssc, significantly elevated miR-210 level in ECs; 3) EPC-EXsmiR-210 were more effective than EPC-EXs and EPC-EXssc in reducing H/R-induced EC apoptosis, ROS overproduction and angiogenic dysfunction; 4) EPC-EXs decreased mitochondrial fragmentation, elevated MMP and ATP level, as well as improved mitochondrial mfn2 and drp1 dysregulation, which were more effective in EPC-EXsmiR-210. Conclusion: Our results suggest that EPC-EXs protect ECs against H/R injury via improving mitochondrial function and miR-210 enrichment could boost their effects.



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