Highlights
- •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.
Abstract
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.
Conclusion
Endothelial cells exposed in vivo even transiently to hyperglycaemia, oxidative stress
and inflammation exhibit durable pro-atherogenic modifications.
Keywords
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References
- Increased risk of cardiovascular disease in young women following gestational diabetes mellitus.Diabetes Care. 2008 Aug; 31: 1668-1669
- Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus.Diabetes Care. 2004 Jan; 27: 21-27
- Maternal inflammation, growth retardation, and preterm birth: insights into adult cardiovascular disease.Life Sci. 2011 Sep 26; 89: 417-421
- Maternal diabetes in pregnancy: early and long-term outcomes on the offspring and the concept of “metabolic memory”.Exp Diabetes Res. 2011; 2011: 218598
- Gestational diabetes and subclinical inflammation: evaluation of first year postpartum outcomes.Diabetes Res Clin Pract. 2011 Dec; 94: 426-433
- Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population.Nutr Metab Cardiovasc Dis. 2012 Jan; 22: 50-57
- Impact of glycemic variability on cardiovascular outcomes beyond glycated hemoglobin. Evidence and clinical perspectives.Nutr Metab Cardiovasc Dis. 2012 Sep; 22: 691-696
- High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells.Circulation. 1997 Jul 1; 96: 25-28
- Elevated D-glucose induces insulin insensitivity in human umbilical endothelial cells isolated from gestational diabetic pregnancies.J Physiol. 1998 Jan 1; 506: 219-230
- New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy.Diabetes Care. 2003 May; 26: 1589-1596
- Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells.Eur J Pharmacol. 2007 Jul 2; 566: 1-10
- Increased endothelial inflammation, sTie-2 and arginase activity in umbilical cords obtained from gestational diabetic mothers.PLoS One. 2013; 8 (e84546)
- Foxo1 links hyperglycemia to LDL oxidation and endothelial nitric oxide synthase dysfunction in vascular endothelial cells.Diabetes. 2009 Oct; 58: 2344-2354
- Increased atherosclerosis and endothelial dysfunction in mice bearing constitutively deacetylated alleles of foxo1 gene.J Biol Chem. 2012 Apr 20; 287: 13944-13951
- Early subclinical atherosclerosis in women with previous gestational diabetes mellitus.Diabetes Care. 2008 May; 31: e32
- Nitric oxide attenuates adhesion molecule expression in human endothelial cells.Cytokine. 1996 Nov; 8: 817-821
- Oxidative stress and increased eNOS and NADPH oxidase expression in mouse microvessel endothelial cells.J Cell Physiol. 2007 Sep; 212: 682-689
- High glucose causes upregulation of cyclooxygenase-2 and alters prostanoid profile in human endothelial cells: role of protein kinase C and reactive oxygen species.Circulation. 2003 Feb 25; 107: 1017-1023
- Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure.Cardiovasc Res. 1999 Aug 15; 43: 562-571
- Effects of diabetes on plasma nitrotyrosine levels.Diabet Med. 2004 Jun; 21: 577-580
- Protein oxidation markers in women with and without gestational diabetes mellitus: a possible relation with paraoxonase activity.Diabetes Res Clin Pract. 2011 Dec; 94: 404-409
- Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and thrombosis activation in type 1 diabetes and in healthy controls.Nutr Metab Cardiovasc Dis. 2014 Feb; 24: 116-123
- Dysfunction of the endothelial nitric oxide signalling pathway in diabetes and hyperglycaemia.Exp Physiol. 1997 May; 82: 423-452
- Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice.Cardiovasc Diabetol. 2005; 4: 5
- 10-year follow-up of intensive glucose control in type 2 diabetes.N Engl J Med. 2008 Oct 9; 359: 1577-1589
- Offspring of diabetic pregnancy: long-term outcomes.Semin Fetal Neonatal Med. 2009 Apr; 14: 119-124
- Epigenetic mechanisms that underpin metabolic and cardiovascular diseases.Nat Rev Endocrinol. 2009 Jul; 5: 401-408
- Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia.J Exp Med. 2008 Sep 29; 205: 2409-2417
- Epigenetic regulation of endothelial lineage committed genes in pro-angiogenic hematopoietic and endothelial progenitor cells.Circ Res. 2011 Nov 11; 109: 1219-1229
- High Glucose effects on eNOS and SIRT1 expression and chromatin acetylation in endothelial cells.Diabetologia. 2012; 55 ([Meeting Abstract]): S506
Article info
Publication history
Published online: July 03, 2014
Accepted:
June 15,
2014
Received in revised form:
June 10,
2014
Received:
January 24,
2014
Identification
Copyright
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
