Umbilical cord mesenchymal stem cell exosomal miR-143-3p delays endothelial cell senescence through targeting COX-2.

Abstract

Senescence of vascular endothelial cells leads to endothelial dysfunction and exacerbates atherosclerosis. In this study, we presented evidence that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos) could delay endothelial cell senescence, promote endothelial cell proliferation, and enhance angiogenic activity in vitro. The miRNA profiling analysis revealed a high expression of miR-143-3p in hucMSC-Exos, which was further upregulated in endothelial cells treated with hucMSC-Exos. Silencing miR-143-3p induced endothelial cell senescence, as evidenced by increased senescence-associated β-galactosidase activity, reduced cell proliferation, and inhibited tubular formation; conversely, overexpression of miR-143-3p exhibited opposite effects. Moreover, we found that miR-143-3p directly targeted Cyclooxygenase-2 (COX-2) and suppressed its translation, thus delaying endothelial cell senescence. These results suggested that hucMSC-Exos can delay endothelial cell senescence by transferring miR-143-3p. In summary, our data demonstrated the potential of hucMSC-Exos as an intervention against vascular aging.