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Features of endothelial dysfunction in umbilical cord vessels of women with gestational diabetes.

AbstractBACKGROUND 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 GDMand 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 O(-)(2)egeneration 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.
CONCLUSION:
Endothelial cells exposed in vivo even transiently to hyperglycaemia, oxidative stress and inflammation exhibit durable pro-atherogenic modifications.
AuthorsP Di Fulvio, A Pandolfi, G Formoso, S Di Silvestre, P Di Tomo, A Giardinelli, A De Marco, N Di Pietro, M Taraborrelli, S Sancilio, R Di Pietro, M Piantelli, A Consoli
JournalNutrition, metabolism, and cardiovascular diseases : NMCD (Nutr Metab Cardiovasc Dis) Vol. 24 Issue 12 Pg. 1337-45 (Dec 2014) ISSN: 1590-3729 [Electronic] Netherlands
PMID25438716 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Glucose
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Cyclic AMP
  • Nitric Oxide Synthase Type III
Topics
  • Adult
  • Atherosclerosis (pathology)
  • Blood Glucose (metabolism)
  • Cell Adhesion
  • Cyclic AMP (metabolism)
  • Diabetes, Gestational (pathology)
  • Female
  • Glucose Tolerance Test
  • Homeostasis
  • Human Umbilical Vein Endothelial Cells (pathology)
  • Humans
  • Hyperglycemia (blood)
  • Leukocytes
  • Nitric Oxide (metabolism)
  • Nitric Oxide Synthase Type III (metabolism)
  • Oxidative Stress
  • Pregnancy
  • Tyrosine (analogs & derivatives, metabolism)
  • Umbilical Cord (pathology)
  • Vascular Diseases (complications, pathology)

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