Fetoplacental endothelial exosomes modulate high d-glucose-induced endothelial dysfunction. (June 2018)

• Record Type: Journal Article
• Authors: Sáez, Tamara; de Vos, Paul; Kuipers, Jeroen; Sobrevia, Luis; Faas, Marijke M.
• Is Part Of: Placenta. Volume 66(2018)
• Page Start: 26
• Page End: 35
• Publication Date: 2018-06
• Subjects: Exosomes -- Gestational diabetes -- High glucose -- Fetoplacental vasculature -- Endothelial dysfunction; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2018.04.010
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with fetoplacental endothelial dysfunction, which may be induced by hyperglycemia. We hypothesized that endothelial exosomes, which are extracellular nanovesicles affecting endothelial function, play a role in the high glucose (HG)-induced endothelial dysfunction. METHODS: Exosomes were isolated from HUVECs incubated with basal glucose (5.5 mmol/L; HUVEC- BG; exo-BG) and from HUVECs incubated with HG for 24 h (25 mmol/L; HUVEC-HG; exo-HG) in exosome-free medium. Exosomes were isolated and characterized by ultracentrifugation, sucrose gradient, electron microscopy, nanotracking analysis and Western blotting. HUVEC-BG and HUVEC-HG were exposed to exo-BG and exo-HG in two different concentrations: 5 μg and 1 μg exosome protein/mL. The exosomal effect on endothelial cell function was determined by wound healing assay, expression of endothelial nitric oxide synthase (eNOS), human cationic amino acid transporter type 1 (hCAT-1), vascular endothelial growth factor (VEGF) and intracellular adhesion molecule type 1 (ICAM-1) by Western blotting, qPCR or flow cytometry. RESULTS: HG increased the exosomal release from HUVECs, endothelial wound healing and expression of phosphorylated (P∼Ser 1177 )-eNOS, hCAT-1, VEGF and ICAM-1. Exo-HG also increased endothelial cell wound healing, P∼Ser 1177 -eNOS, hCAT-1 and ICAM-1 expression in HUVEC-BG. Exo-BG reverted the effect of HG on endothelial cell wound healing and hCAT-1 mRNA expression to normal values. DISCUSSION: Our results show that HG may induce endothelial dysfunction in HUVECs and that exosomes from HUVEC-HG mimicked some of the effects of HG. This study contributes to the unraveling of the mechanism by which hyperglycemia affects the fetoplacental vasculature in GDM. Highlights: HG induced changes associated to endothelial dysfunction and activation in HUVECs. HG increased exosome release from HUVECs. Exosomes from HUVECs exposed to HG induced similar changes associated with HG.