ArticleThe Journal of cell biology2003
Elevated glucose inhibits VEGF-A-mediated endocardial cushion formation: modulation by PECAM-1 and MMP-2.
Article in The Journal of cell biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Genetic variation in VEGF does not contribute significantly to the risk of congenital cardiovascular malformation.PloS one · 2009Pooled it
- Impact of genetic factors on antioxidant rescue of maternal diabetes-associated congenital heart disease.JCI insight · 2024Article
- Differential Development of the Chordae Tendineae and Anterior Leaflet of the Bovine Mitral Valve.Journal of cardiovascular development and disease · 2024Article
- CD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer's disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- The epicardium obscures interpretations on endothelial-to-mesenchymal transition in the mouse atrioventricular canal explant assay.Scientific reports · 2018Article
- Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis.American journal of obstetrics and gynecology · 2016Article
- Endocardial-to-mesenchymal transformation and mesenchymal cell colonization at the onset of human cardiac valve development.Development (Cambridge, England) · 2016Article
- Inhibition of lung tumor growth in nude mice by siRNAOncology letters · 2014Article
- CD44 regulation of endothelial cell proliferation and apoptosis via modulation of CD31 and VE-cadherin expression.The Journal of biological chemistry · 2014Article
- Allelic Interaction betweenAIMS genetics · 2014Article
- Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease.Circulation research · 2012Review
- The role of immunoglobulin superfamily cell adhesion molecules in cancer metastasis.International journal of cell biology · 2012Article
- What chick and mouse models have taught us about the role of the endocardium in congenital heart disease.Birth defects research. Part A, Clinical and molecular teratology · 2011Review
- Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions.The Journal of biological chemistry · 2010Article
- Arsenic exposure perturbs epithelial-mesenchymal cell transition and gene expression in a collagen gel assay.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
- Activated protein C enhances cell motility of endothelial cells and MDA-MB-231 breast cancer cells by intracellular signal transduction.Experimental cell research · 2010Article
- VEGF-A and Semaphorin3A: modulators of vascular sympathetic innervation.Developmental biology · 2009Article
- Article
- A novel matrix metalloproteinase 2 (MMP2) terminal hemopexin domain mutation in a family with multicentric osteolysis with nodulosis and arthritis with cardiac defects.European journal of human genetics : EJHG · 2009Article
- Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development.Developmental dynamics : an official publication of the American Association of Anatomists · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Atrioventricular (AV) septal defects resulting from aberrant endocardial cushion (EC) formation are observed at increased rates in infants of diabetic mothers. EC formation occurs via an epithelial-mesenchymal transformation (EMT), involving transformation of endocardial cells into mesenchymal cells, migration, and invasion into extracellular matrix. Here, we report that elevated glucose inhibits EMT by reducing myocardial vascular endothelial growth factor A (VEGF-A). This effect is reversed with exogenous recombinant mouse VEGF-A165, whereas addition of soluble VEGF receptor-1 blocks EMT. We show that disruption of EMT is associated with persistence of platelet endothelial cell adhesion molecule-1 (PECAM-1) and decreased matrix metalloproteinase-2 (MMP-2) expression. These findings correlate with retention of a nontransformed endocardial sheet and lack of invasion. The MMP inhibitor GM6001 blocks invasion, whereas explants from PECAM-1 deficient mice exhibit MMP-2 induction and normal EMT in high glucose. PECAM-1-negative endothelial cells are highly motile and express more MMP-2 than do PECAM-1-positive endothelial cells. During EMT, loss of PECAM-1 similarly promotes single cell motility and MMP-2 expression. Our findings suggest that high glucose-induced inhibition of AV cushion morphogenesis results from decreased myocardial VEGF-A expression and is, in part, mediated by persistent endocardial cell PECAM-1 expression and failure to up-regulate MMP-2 expression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.