title: Increased placental expression of tissue factor is associated with abnormal uterine and umbilical Doppler waveforms in severe preeclampsia with fetal growth restriction.
abstract: BACKGROUND
  This study investigated whether modifications of placental expression of endothelin-1 (ET-1), nitric oxide synthase (NOS) and tissue factor (TF) are associated with abnormal Doppler waveforms.
  
  
  METHODS
  Fourteen pre-term severe preeclamptic (PE) women with fetal growth restriction (FGR) and 14 normal preg nant women underwent serial Doppler examination of the uterine and umbilical arteries (UA). Placental ET-1 and T expression was evaluated by in situ hybridization, NOS by NADPH-diaforase staining and in situ hybridization Doppler evaluation was extended to 11 female kidney transplant recipients (Tx), without FGR and/or PE, in wh we previously demonstrated a strong modification of placental ET-1/NOS vasoactive balance.
  
  
  RESULTS
  PE women showed a marked reduction of endothelial constitutive NOS (ecNOS) expression in the syncy tiotrophoblast layer of all villi, whereas ET-1 expression was unchanged. All cases showed abnormal uterine artery blood flow velocimetry, 13 out of 14 PE women showed abnormal UA Doppler waveforms. In contrast, all Tx women showed normal UA blood velocimetry, all but one woman displayed a normal uterine artery waveform pattern. The Doppler velocimetry abnormalities were significantly associated with only TF expression, which was markedly increased, exclusively, in the endothelial cells within the basal decidua of PE women.
  
  
  CONCLUSIONS
  The modification of ET-1/NOS vasoactive balance, per se, did not lead to Doppler impedance modifica tions in the UA and uterine arteries, observed in pre-term PE women with FGR. Instead, Doppler velocimetry modi fications appeared to correlate with endothelial cell activation, as revealed by increased TF expression.
authors.affiliation: Department of Emergency and Organ Transplant, Division of Nephrology, University of Bari, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Paolo
authors.forename: Paolo
authors.initials: P
authors.lastname: Volpe
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stallone
authors.forename: Antonio
authors.initials: A
authors.lastname: Schena
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Greco
authors.forename: Leonardo
authors.initials: L
authors.lastname: Resta
authors.forename: Luigi
authors.initials: L
authors.lastname: Selvaggi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cincione
authors.forename: F Paolo
authors.initials: FP
authors.lastname: Schena
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression; D006651:Histocytochemistry; D006801:Humans; D017403:In Situ Hybridization; D016030:Kidney Transplantation; D009252:NADPH Dehydrogenase; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D013194:Staining and Labeling; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D018608:Ultrasonography, Doppler; D014470:Umbilical Cord / Q000000981:diagnostic imaging*; D014599:Uterus / Q000098:blood supply*
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D013925:Thromboplastin; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase