title: Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta.
abstract: OBJECTIVE
  Soluble vascular endothelial growth factor receptor-1 (also know as soluble fms-like tyrosine kinase [sFlt]-1) is a key causative factor of preeclampsia. Resveratrol, a plant phytoalexin, has antiinflammatory and cardioprotective properties. We sought to determine the effect of resveratrol on sFlt-1 release.
  
  
  METHODS
  Human umbilical vein endothelial cells, transformed human trophoblast-8 (HTR/SVneo)-8/SVneo trophoblast cells, or placental explants were incubated with cytokines and/or resveratrol. Conditioned media were assayed for sFlt-1 by enzyme-linked immunosorbent assay and cell proteins used for Western blotting.
  
  
  RESULTS
  Resveratrol inhibited cytokine-induced release of sFlt-1 from normal placental explants and from preeclamptic placental explants. Preincubation of human umbilical vein endothelial cells or HTR-8/SVneo cells with resveratrol abrogated sFlt-1 release. Resveratrol prevented the up-regulation of early growth response protein-1 (Egr-1), a transcription factor necessary for induction of the vascular endothelial growth factor receptor-1 gene and caused up-regulation of heme oxygenase-1, a cytoprotective enzyme found to be dysfunctional in preeclampsia.
  
  
  CONCLUSIONS
  In summary, resveratrol can inhibit sFlt-1 release and up-regulate heme oxygenase-1; thus, may offer therapeutic potential in preeclampsia.
authors.affiliation: University/British Heart Foundation Center for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Cudmore
authors.forename: Wenda
authors.initials: W
authors.lastname: Ramma
authors.forename: Meng
authors.initials: M
authors.lastname: Cai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Shakil
authors.initials: S
authors.lastname: Ahmad
authors.forename: Bahjat
authors.initials: B
authors.lastname: Al-Ani
authors.forename: Asif
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000201:enzymology; D011247:Pregnancy; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016207:Cytokines; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D004791:Enzyme Inhibitors; D013267:Stilbenes; D051547:Heme Oxygenase-1; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D000077185:Resveratrol