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

Microcirculation. 2019 Jan;26(1):e12515. doi: 10.1111/micc.12515. Epub 2018 Nov 29.

Abstract

Objective: To investigate the effects of TNF-α-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-α. HUVECs were treated with or without TNF-α, or different concentrations of exosomes isolated from conditioned media with or without TNF-α induction (TExo and CExo , respectively).

Results: The results showed that TNF-α significantly inhibited migration, tube formation, and increased apoptosis rate of HUVECs compared with controls. Furthermore, TNF-α-induced exosomes (TExo ) rather than CExo , indicated similar effects to inhibit migration, tube formation and promote endothelial apoptosis. Although TNF-α treatment did not show a statistical difference, TExo significantly inhibited extracellular OCR compared with controls. TExo could significantly inhibited intracellular OCR in a hypoxia condition. TNF-α significantly increased L-ECA compared with control cells, and TExo showed similar stimulative effect on L-ECA.

Conclusions: TNF-α-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.

Keywords: TNF-α; bioenergetics; cell behavior; endothelial cells; exosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Movement
  • Cells, Cultured
  • Energy Metabolism
  • Exosomes / drug effects
  • Exosomes / physiology*
  • Glycolysis
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Human Umbilical Vein Endothelial Cells / physiology
  • Human Umbilical Vein Endothelial Cells / ultrastructure
  • Humans
  • Hypoxia
  • Lactic Acid / metabolism
  • Oxygen Consumption
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Tumor Necrosis Factor-alpha
  • Lactic Acid