Effects of tumor necrosis factor-α-induced exosomes on the endothelial cellular behavior, metabolism and bioenergetics

Objective To investigate the effects of TNF-alpha-induced exosomes release on the biological behavior, metabolism, and bioenergetics of HUVECs. Methods Exosomes were isolated from conditioned media of HUVECs by ultracentrifugation after treatment with or without TNF-alpha. HUVECs were treated with or without TNF-alpha, or different concentrations of exosomes isolated from conditioned media with or without TNF-alpha induction (T-Exo and C-Exo, respectively). Results The results showed that TNF-alpha significantly inhibited migration, tube formation, and increased apoptosis rate of HUVECs compared with controls. Furthermore, TNF-alpha-induced exosomes (T-Exo) rather than C-Exo, indicated similar effects to inhibit migration, tube formation and promote endothelial apoptosis. Although TNF-alpha treatment did not show a statistical difference, T-Exo significantly inhibited extracellular OCR compared with controls. T-Exo could significantly inhibited intracellular OCR in a hypoxia condition. TNF-alpha significantly increased L-ECA compared with control cells, and T-Exo showed similar stimulative effect on L-ECA. Conclusions TNF-alpha-induced exosomes could significantly (a) change migration, tube formation, and apoptosis; (b) inhibit endothelial extracellular OCR and intracellular OCR (hypoxia); (c) increase glycolysis rate of the endothelial cells. These data provide new evidence for exploring endothelial behavior regulation using exosomes and their effects on endothelial metabolism and bioenergetics.