title: Vascular pool of releasable soluble VEGF receptor-1 (sFLT1) in women with previous preeclampsia and uncomplicated pregnancy.
abstract: BACKGROUND
  Research examining the source of excess soluble fms-like tyrosine kinase 1 (sFLT1) in preeclampsia has focused on the placenta. The potential contribution of the releasable store of sFLT1 in the systemic vasculature is unknown.
  
  
  OBJECTIVE
  We asked whether the nonplacental releasable store of sFLT1 is larger in women with previous preeclampsia than in women with a previous uncomplicated pregnancy.
  
  
  METHODS
  We administered heparin to nulligravid women and to women with previous preeclampsia or a previous uncomplicated pregnancy. We compared post-heparin sFLT1 concentrations with those observed in uncomplicated pregnancy and preeclampsia.
  
  
  METHODS
  The study was performed at Magee-Womens Hospital.
  
  
  METHODS
  Participants included nulligravidas (n = 8), women 6-24 months postpartum (previous uncomplicated pregnancy, n = 16; previous preeclampsia, n = 15), and pregnant women (uncomplicated pregnancy, n = 30; preeclampsia, n = 25).
  
  
  METHODS
  Nonpregnant women received an unfractionated heparin bolus.
  
  
  METHODS
  Pre- and post-heparin plasma sFLT1, placental growth factor, and vascular endothelial growth factor were measured.
  
  
  RESULTS
  In nonpregnant women, heparin increased plasma sFLT1 by 250-fold (P < .01), increased placental growth factor by 7-fold (P < .01), and decreased free vascular endothelial growth factor (P < .01). These changes did not differ between nulligravidas, women with previous preeclampsia, and women with a previous uncomplicated pregnancy. Post-heparin sFLT1 in nonpregnant women was higher than sFLT1 in uncomplicated pregnancy, but lower than sFLT1 in preeclampsia. Baseline and post-heparin sFLT1 were positively correlated (r(2) = 0.19; P < .01). Heparin increased the concentration of the 100-kDa sFLT1 isoform. Adding heparin to whole blood or plasma did not increase sFLT1.
  
  
  CONCLUSIONS
  Nonpregnant women have a significant vascular store of releasable sFLT1. The size of this store does not differ between women with previous preeclampsia vs women with previous uncomplicated pregnancy.
authors.affiliation: Division of Nephrology and Hypertension (T.L.W.), Mayo Clinic, Rochester, Minnesota 55905; Beth Israel Deaconess Medical Center (A.R.), Boston, Massachusetts 02215; Magee-Womens Research Institute (A.C.M., L.R.E., R.W.P., J.M.R., R.E.G., C.A.H.), and Department of Obstetrics, Gynecology, and Reproductive Sciences (R.W.P., J.M.R., C.A.H.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Department of Environmental and Occupational Health (R.E.G., C.A.H.), and Department of Epidemiology (J.M.R.), Graduate School of Public Health (J.M.R.), University of Pittsburgh, Pittsburgh, Pennsylvania 15261; and Clinical and Translational Science Institute (J.M.R.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Weissgerber
authors.forename: Augustine
authors.initials: A
authors.lastname: Rajakumar
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Myerski
authors.forename: Lia R
authors.initials: LR
authors.lastname: Edmunds
authors.forename: Robert W
authors.initials: RW
authors.lastname: Powers
authors.forename: James M
authors.initials: JM
authors.lastname: Roberts
authors.forename: Robin E
authors.initials: RE
authors.lastname: Gandley
authors.forename: Carl A
authors.initials: CA
authors.lastname: Hubel
mesh_terms: D000328:Adult; D005260:Female; D020073:Gravidity; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D010298:Parity; D049590:Postpartum Period / Q000097:blood* / Q000187:drug effects; D011225:Pre-Eclampsia / Q000097:blood* / Q000517:prevention & control; D011247:Pregnancy / Q000097:blood*; D017584:Reproductive History; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D006493:Heparin; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1