title: Microvascular endothelial cell activation is present in the umbilical placental microcirculation in fetal placental vascular disease.
abstract: OBJECTIVE
  Fetal growth restriction is associated with an abnormal umbilical artery Doppler study. A vascular disease is present in the fetal umbilical placental microcirculation. We hypothesized that the local production of factors that are injurious to microvessel endothelium is responsible for this vascular disease and that endothelial cell activation is a feature of this. Because the expression of the cell adhesion molecules is associated with endothelial cell activation, we isolated endothelial cells from the microvessels of the umbilical placenta and examined them for evidence of gene expression of cell adhesion molecules.
  
  
  METHODS
  Endothelial cells from the microcirculation of human placenta were isolated and purified with collagenase digestion and extraction with superparamagnetic beads that were coated with monoclonal antibody against CD31. Microvessel endothelial cells were isolated from the placentae of 13 women with a normal pregnancy and delivery at term and 10 placentas with umbilical placental vascular disease that was defined by abnormal umbilical artery Doppler study. Total RNA was extracted from isolated endothelial cells. The messenger RNA expressions of cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and platelet endothelial cell adhesion molecule-1) were assessed by semiquantitative reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Microvessel endothelial cells from the fetal placentae of pregnancies that were complicated by umbilical placental vascular disease showed an enhanced expression of intercellular adhesion molecule-1 messenger RNA (2.12+/-0.45 vs 0.92+/-0.25) and platelet endothelial cell adhesion molecule-1 messenger RNA (4.29+/-0.87 vs 2.41+/-0.42) in comparison to normal pregnancies. There was no significant difference in expression of vascular cell adhesion molecule-1 messenger RNA (1.55+/-0.37 vs 1.68+/-0.38).
  
  
  CONCLUSIONS
  We have shown that vascular disease in the fetal umbilical placental circulation is associated with an increase in the expression of intercellular adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 by microvessel endothelial cells. We postulate that locally released factors cause injury and activation to microvessel endothelial cells. In this regard, the process in the fetus is similar to that of atherothrombotic vascular disease of later life.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Sydney at Westmead Hospital, Sydney, 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; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008833:Microcirculation; D010920:Placenta / Q000098:blood supply*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D011256:Pregnancy Outcome; D012333:RNA, Messenger / Q000378:metabolism; D014470:Umbilical Cord / Q000098:blood supply*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D014652:Vascular Diseases / Q000503:physiopathology*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1