- •HUVEC from Control and Gestational Diabetic mothers were compared.
- •Diabetic HUVEC exhibited impaired NO bioavailability.
- •Diabetic HUVEC showed increased monocyte adhesion to endothelium, leucocyte adhesion molecule expression and exposure on plasma membrane.
- •Diabetic HUVEC cultured in vitro at physiological conditions exhibit durable pro-atherogenic modification.
Background and aims
Gestational diabetes (GDM) is associated with increased oxidative stress and overexpression of inflammatory cytokines, both of which might lead to endothelial dysfunction and vascular disease. As such, GDM could be viewed as a sort of ‘short lived’ metabolic syndrome. As umbilical cord vessels represent a suitable model for the study of vascular alterations brought about by GDM, the aim of the present work was to characterize the phenotype of human umbilical vein endothelial cells (HUVECs) chronically exposed to hyperglycaemia and to a pro-inflammatory environment during pregnancy so as to identify molecular modifications of cellular homoeostasis eventually impacting on endothelial dysfunction.
Methods and result
Tissue specimens and HUVECs were obtained from umbilical cords of GDM and control women. As compared to controls, GD-HUVEC exhibited enhanced monocyte adhesion and vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression and exposure on plasma membrane after tumour necrosis factor-alpha (TNF-α) stimulation (Western blot, flow cytometer). As compared to control cells, GD-HUVEC in basal conditions exhibited enhanced monocyte adhesion, nitric oxide synthase (NOS) expression and activity (eNOS Real-Time polymerase chain reaction, Western Blot for eNOS total protein and monomers/dimers ratio, conversion of [3H]-L-arginine in [3H]-L-citrulline), increased O2– generation together with increased NT levels (immunofluorescence) and reduced NO bioavailability (guanosine 3′,5′-monophosphate (cGMP) production, EIA). Furthermore, immunohistochemistry revealed increased eNOS and NT immunoreactivity in GD umbilical cords.
Endothelial cells exposed in vivo even transiently to hyperglycaemia, oxidative stress and inflammation exhibit durable pro-atherogenic modifications.
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Published online: July 03, 2014
Accepted: June 15, 2014
Received in revised form: June 10, 2014
Received: January 24, 2014
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.