title: Hypoxia activates the human placental vascular endothelial growth factor system in vitro and in vivo: up-regulation of vascular endothelial growth factor in clinically relevant hypoxic ischemia in birth asphyxia.
abstract: OBJECTIVE
  We investigated the influence of acute hypoxia on the placental vascular endothelial growth factor system in vitro and in vivo in acute birth asphyxia compared with pregnancies that were complicated by preeclampsia and with healthy control subjects.
  
  
  METHODS
  Messenger RNA levels for vascular endothelial growth factor, flt-1, and KDR were measured by TaqMan real-time polymerase chain reaction in human placental choriocarcinoma cells (BeWo) that were exposed to hypoxia (1% oxygen, 5% carbon dioxide, 94% nitrogen) and in placental tissue of neonates with birth asphyxia (n = 20), newborn infants of mothers with preeclampsia (n = 20), and gestational age-matched control subjects. Immunhistologically, placental vascular endothelial growth factor protein expression was compared among the groups.
  
  
  RESULTS
  In BeWo cells, vascular endothelial growth factor, flt-1 and KDR messenger RNA increased in a time-dependent manner in response to hypoxia. In vivo, vascular endothelial growth factor/beta-actin and KDR/beta-actin messenger RNA were significantly higher in placental tissue of newborn infants with severe hypoxic-ischemic encephalopathy than with newborn infants with mild or no hypoxic-ischemic encephalopathy and control subjects. In chronic placental hypoxia (preeclampsia), vascular endothelial growth factor and both receptors were found to be up-regulated. Increased placental vascular endothelial growth factor expression was confirmed by immunohistologic examination.
  
  
  CONCLUSIONS
  The vascular endothelial growth factor system is up-regulated in response to placental hypoxia and is assumed to be a potential early indicator of severe birth asphyxia.
authors.affiliation: Department of Pediatrics, University of Erlangen-Nuernberg, Germany. regina.trollmann@kinder.imed.uni-erlangen.de
authors.forename: R
authors.initials: R
authors.lastname: Trollmann
authors.forename: K
authors.initials: K
authors.lastname: Amann
authors.forename: E
authors.initials: E
authors.lastname: Schoof
authors.forename: E
authors.initials: E
authors.lastname: Beinder
authors.forename: D
authors.initials: D
authors.lastname: Wenzel
authors.forename: W
authors.initials: W
authors.lastname: Rascher
authors.forename: J
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D000199:Actins / Q000235:genetics; D001238:Asphyxia Neonatorum / Q000378:metabolism*; D035061:Control Groups; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D042442:Vascular Endothelial Growth Factors
chemical_list: D000199:Actins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2