Linked Life Data

18469803

Source:http://linkedlifedata.com/resource/pubmed/id/18469803

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7198
pubmed:dateCreated
2008-6-19
pubmed:abstractText
Despite intense investigation, mechanisms that facilitate the emergence of the pre-eclampsia phenotype in women are still unknown. Placental hypoxia, hypertension, proteinuria and oedema are the principal clinical features of this disease. It is speculated that hypoxia-driven disruption of the angiogenic balance involving vascular endothelial growth factor (VEGF)/placenta-derived growth factor (PLGF) and soluble Fms-like tyrosine kinase-1 (sFLT-1, the soluble form of VEGF receptor 1) might contribute to some of the maternal symptoms of pre-eclampsia. However, pre-eclampsia does not develop in all women with high sFLT-1 or low PLGF levels, and it also occurs in some women with low sFLT-1 and high PLGF levels. Moreover, recent experiments strongly suggest that several soluble factors affecting the vasculature are probably elevated because of placental hypoxia in the pre-eclamptic women, indicating that upstream molecular defect(s) may contribute to pre-eclampsia. Here we show that pregnant mice deficient in catechol-O-methyltransferase (COMT) show a pre-eclampsia-like phenotype resulting from an absence of 2-methoxyoestradiol (2-ME), a natural metabolite of oestradiol that is elevated during the third trimester of normal human pregnancy. 2-ME ameliorates all pre-eclampsia-like features without toxicity in the Comt(-/-) pregnant mice and suppresses placental hypoxia, hypoxia-inducible factor-1alpha expression and sFLT-1 elevation. The levels of COMT and 2-ME are significantly lower in women with severe pre-eclampsia. Our studies identify a genetic mouse model for pre-eclampsia and suggest that 2-ME may have utility as a plasma and urine diagnostic marker for this disease, and may also serve as a therapeutic supplement to prevent or treat this disorder.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
453
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1117-21
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18469803-Albumins, pubmed-meshheading:18469803-Animals, pubmed-meshheading:18469803-Anoxia, pubmed-meshheading:18469803-Blood Pressure, pubmed-meshheading:18469803-Catechol O-Methyltransferase, pubmed-meshheading:18469803-Creatinine, pubmed-meshheading:18469803-Disease Models, Animal, pubmed-meshheading:18469803-Estradiol, pubmed-meshheading:18469803-Female, pubmed-meshheading:18469803-Humans, pubmed-meshheading:18469803-Hypertension, pubmed-meshheading:18469803-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:18469803-Killer Cells, Natural, pubmed-meshheading:18469803-Litter Size, pubmed-meshheading:18469803-Male, pubmed-meshheading:18469803-Mice, pubmed-meshheading:18469803-Placenta, pubmed-meshheading:18469803-Pre-Eclampsia, pubmed-meshheading:18469803-Pregnancy, pubmed-meshheading:18469803-Proteinuria, pubmed-meshheading:18469803-Vascular Endothelial Growth Factor Receptor-1
pubmed:year
2008
pubmed:articleTitle
Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia.
pubmed:affiliation
Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural