Extracellular vesicle glucose transporter-1 and glycan features in monocyte-endothelial inflammatory interactions

Monocyte-induced endothelial cell inflammation is associated with multiple pathological conditions, and extracellular vesicles (EVs) are essential nanosized components of intercellular communication. EVs derived from endotoxin-stimulated monocytes were previously shown to carry pro-inflammatory proteins and RNAs. The role of glucose transporter-1 (GLUT-1) and glycan features in monocyte-derived EV-induced endothelial cell inflammation remains largely unexplored. This study demonstrates that EVs derived from endotoxin-stimulated monocytes activate inflammatory pathways in endothelial cells, which are partially attributed to GLUT-1. Alterations in glycan features and increased levels of GLUT-1 were observed in EVs derived from endotoxin-stimulated monocytes. Notably, inhibition of EV-associated GLUT-1, through the use of fasentin, suppressed EV-induced inflammatory cytokines in recipient endothelial cells. Endotoxin stimulation of THP-1 monocytes produces extracellular vesicles (EVs) in greater number, with higher expression of glucose transporter-1 (GLUT-1) and glycosylation changes. These stimulated EVs induce inflammatory cytokine and membrane adhesion molecule expression in human umbilical vein endothelial cells (HUVECs), some of which can be mitigated by the GLUT-1 inhibitor fasentin. [Display omitted]