ArticleDiabetologia2004
Vascular endothelial cadherin and beta-catenin in human fetoplacental vessels of pregnancies complicated by Type 1 diabetes: associations with angiogenesis and perturbed barrier function.
Article in Diabetologia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 60 citations in OpenAlex.
- Umbilical cord mesenchymal stem cells from gestational diabetes show impaired ability to up-regulate paracellular permeability from sub-endothelial niche.Clinical science (London, England : 1979) · 2024Article
- Development of an SPRi Test for the Quantitative Detection of Cadherin 12 in Human Plasma and Peritoneal Fluid.International journal of molecular sciences · 2023Article
- Mechanistic insights into the development of severe fetal growth restriction.Clinical science (London, England : 1979) · 2023Review
- Review
- Placental expression of glucose transporters GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in pregnancies complicated by gestational and type 1 diabetes mellitus.Journal of diabetes investigation · 2022Article
- Altered protein O-GlcNAcylation in placentas from mothers with diabetes causes aberrant endocytosis in placental trophoblast cells.Scientific reports · 2021Article
- Compromised barrier integrity of human feto-placental vessels from gestational diabetic pregnancies is related to downregulation of occludin expression.Diabetologia · 2021Article
- FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.Frontiers in endocrinology · 2021Article
- Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors.Molecular medicine reports · 2020Article
- Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-AClinical science (London, England : 1979) · 2017Article
- Tacrolimus in the prevention of adverse pregnancy outcomes and diabetes-associated embryopathies in obese and diabetic mice.Journal of translational medicine · 2017Article
- Article
- Fibrinogen-like protein 2 gene silencing inhibits cardiomyocytes apoptosis, improves heart function of streptozotocin-induced diabetes rats and the molecular mechanism involved.Bioscience reports · 2015Article
- Effects of maternal diabetes on trophoblast cells.World journal of diabetes · 2015Review
- Immunohistochemical distribution of cell cycle proteins p27, p57, cyclin D3, PCNA and Ki67 in normal and diabetic human placentas.Journal of molecular histology · 2014Article
- Glucose, insulin, and oxygen interplay in placental hypervascularisation in diabetes mellitus.BioMed research international · 2014Review
- Vascular dysfunction in the diabetic placenta: causes and consequences.Journal of anatomy · 2009Review
- Insulin and the IGF system in the human placenta of normal and diabetic pregnancies.Journal of anatomy · 2009Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIncreased angiogenesis of fetoplacental vessels is a feature of pregnancies complicated by Type 1 diabetes mellitus, but the underlying molecular mechanisms are unknown. This investigation tests whether the diabetic maternal environment alters the phenotypic expression of placental vascular endothelial cadherin and beta-catenin, which have been implicated as key molecules in barrier formation and angiogenesis in the endothelium.
methodsTerm placental microvessels from normal pregnancies (n=8) and from those complicated by Type 1 diabetes (n=8) were perfused with 76-Mr dextran tracers (1 mg/ml) and subjected to immunocytochemistry, immunoblotting and microscopy. Junctional integrity, localisation and phosphorylation were investigated along with total protein levels of vascular endothelial cadherin, beta-catenin and vascular endothelial growth factor. Stereological sampling and estimation tools were used to quantify aspects of angiogenesis and endothelial proliferation.
resultsIn the Type 1 diabetic placentae, junctional localisations of vascular endothelial cadherin and beta-catenin altered significantly, with more than 50% of microvessels showing complete loss of immunoreactivity and with no overall loss of total protein. Tracer leakage was associated with these vessels. There was a two- to three-fold increase in vessels showing junctional phospho-tyrosine immunoreactivity and hyperphosphorylated beta-catenin. Vascular endothelial growth factor levels were higher in these placentae. A four-fold increase in endothelial proliferation was observed, along with an increase in total length of capillaries without any change in luminal diameter. CONCLUSIONS/
interpretationMolecular perturbations of vascular endothelial cadherin and beta-catenin occur in fetoplacental vessels of pregnancies complicated by Type 1 diabetes. Phosphorylation and loss of these molecules from the adherens junctional domains may be influenced in part by the elevated levels of vascular endothelial growth factor in the placenta. Perturbations of the junctional proteins may explain the observed breach in barrier integrity and may contribute to the mechanisms that drive proliferation and increases in capillary length.
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