title: Placental vascular disease and toll-like receptor 4 gene expression.
abstract: OBJECTIVE
  Vascular disease in the placenta, which is identified by the study of umbilical artery Doppler flow velocity waveforms, is associated with endothelial cell activation and a proinflammatory cytokine response in the villous placental circulation. We studied toll-like receptor 4 expression (the ligand is lipopolysaccharide) to examine whether infection may cause these inflammatory components of placental vascular disease through an innate immune response.
  
  
  METHODS
  Microvessel endothelial cells were isolated from human placentae with collagenase digestion and then extracted with Dynabeads that were coated with monoclonal antibody against CD31. We studied 13 placentae from normal pregnancies that were delivered at term and 15 pregnancies with umbilical placental vascular disease that was defined by an abnormal umbilical artery Doppler study. We extracted RNA from the isolated endothelial cells. The messenger RNA expression of toll-like receptor 4 production was assessed by reverse transcriptase-polymerase chain reaction and factored relative to the glyceraldehyde-3-phosphate dehydrogenase and 18S ribosomal RNA genes.
  
  
  RESULTS
  Microvessel endothelial cells from placental villi with placental vascular disease showed up-regulation of toll-like receptor 4 expression (toll-like receptor 4/18S, 1.92 +/- 0.37 vs 0.99 +/- 0.19; P < .05; toll-like receptor 4/glyceraldehyde-3-phosphate dehydrogenase, 2.20 +/- 0.36 vs 1.25 +/- 0.22; P < .05) in comparison with normal pregnancy.
  
  
  CONCLUSIONS
  Up-regulation of toll-like receptor 4 gene in the endothelium of the placental villi is present in placental vascular disease, which may result from exposure of this endothelium to the toll-like receptor 4 ligand lipopolysaccharide in vivo. Directly extracted endothelial cells were used to avoid the possibility for change in behavior in tissue culture. We conclude that Gram-negative infection and lipopolysaccharide stimulation may cause placental vascular disease.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Sydney at Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Neil
authors.initials: N
authors.lastname: Athayde
authors.forename: Brian
authors.initials: B
authors.lastname: Trudinger
mesh_terms: D000328:Adult; D001424:Bacterial Infections / Q000150:complications; D042783:Endothelial Cells / Q000737:chemistry; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D016491:Peripheral Vascular Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology*; D010920:Placenta / Q000098:blood supply; D021041:Placental Circulation / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014463:Ultrasonography; D015854:Up-Regulation
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors