Journal
PLACENTA
Volume 66, Issue -, Pages 26-35Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2018.04.010
Keywords
Exosomes; Gestational diabetes; High glucose; Fetoplacental vasculature; Endothelial dysfunction
Funding
- Fondo Nacional de Desarrollo Cientifico y Tecnologico, Chile [FONDECYT 1150377]
- Marie Curie International Research Staff Exchange Scheme
- 7th European Community Framework Program [295185 - EULAMDIMA]
- Comision Nacional para la Investigacion en Ciencia y Tecnologia (CONICYT) (Chile)
- Abel Tasman Talent program
- University Medical Center Groningen (The Netherlands)
Ask authors/readers for more resources
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 mu g and 1 mu g 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 similar to Ser(1177))-eNOS, hCAT-1, VEGF and ICAM-1. Exo-HG also increased endothelial cell wound healing, P similar to 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available