title: Activation of the receptor for advanced glycation end products system in women with severe preeclampsia.
abstract: BACKGROUND
  Activation of the receptor for advanced glycation end products (RAGE) mediates cellular injury. Soluble forms of RAGE [soluble RAGE (sRAGE), endogenous secretory (esRAGE)] bind RAGE ligands, thereby preventing downstream signaling and damage.
  
  
  OBJECTIVE
  The objective of the study was to characterize the changes in maternal serum, amniotic fluid, and cord blood soluble receptor for advanced glycation end products (sRAGE) during physiological gestation and to provide insight into mechanisms responsible for RAGE activation in preeclampsia.
  
  
  METHODS
  This was a cross-sectional study at a tertiary university hospital.
  
  
  METHODS
  We studied 135 women in the following groups: nonpregnant controls (n = 16), healthy pregnant controls (n = 68), pregnant women with chronic hypertension (n = 13), or pregnant women with severe preeclampsia (sPE; n = 38).
  
  
  METHODS
  sRAGE and esRAGE levels were evaluated in vivo by ELISA in maternal serum, amniotic fluid, and cord blood and in vitro after stimulation of the amniochorion and placental explants with lipopolysaccharide or xanthine/xanthine oxidase. Placenta and amniochorion were immunostained for RAGE. Real-time quantitative PCR measured RAGE mRNA.
  
  
  RESULTS
  Pregnant women had significantly decreased serum sRAGE compared with nonpregnant subjects (P < 0.001). sPE women had higher serum and amniotic fluid sRAGE and esRAGE relative to those expected for gestational age (P < 0.001). Cord blood sRAGE remained unaffected by sPE. RAGE immunoreactivity and mRNA expression appeared elevated in the amniochorion of sPE women. Xanthine/xanthine oxidase (but not lipopolysaccharide) significantly up-regulated the release of sRAGE (P < 0.001) in the amniochorion explant system.
  
  
  CONCLUSIONS
  Fetal membranes are a rich source of sRAGE. Elevated maternal serum and amniotic fluid sRAGE and esRAGE, paralleled by increased RAGE expression in the amniochorion, suggest activation of this system in sPE.
authors.affiliation: Yale University School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, 333 Cedar Street, LLCI 804, New Haven, Connecticut 06520, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Oliver
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.forename: Antonette T
authors.initials: AT
authors.lastname: Dulay
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Baumbusch
authors.forename: Sonya S
authors.initials: SS
authors.lastname: Abdel-Razeq
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Lee
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.forename: Shichu
authors.initials: S
authors.lastname: Jing
authors.forename: Christian M
authors.initials: CM
authors.lastname: Pettker
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000502:physiology; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014969:Xanthine Oxidase / Q000494:pharmacology; D055815:Young Adult
chemical_list: D017127:Glycation End Products, Advanced; D016209:Interleukin-8; D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014969:Xanthine Oxidase