title: Evidence supporting that the excess of the sVEGFR-1 concentration in maternal plasma in preeclampsia has a uterine origin.
abstract: BACKGROUND
  Preeclampsia has been considered an anti-angiogenic state. Two factors have been implicated in the genesis of this state: soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and placental growth factor (PlGF). Indeed, the concentrations of PlGF, an angiogenic factor, are lower in preeclampsia than in normal pregnancy, while the opposite is the case for the anti-angiogenic factor, sVEGFR-1. The source of the excess sVEGFR-1 has not yet been determined. Since the placenta could be a source of sVEGFR-1, we conducted a study to determine whether there is a gradient in the plasma concentration of sVEGFR-1 and PlGF between the uterine vein and the antecubital vein in both patients with preeclampsia and normal pregnant women.
  
  
  METHODS
  A cross-sectional study was performed to determine the plasma concentrations of sVEGFR-1 and PlGF in the uterine and antecubital vein of patients with preeclampsia (n = 9) and normal pregnant women at term (n = 9). Plasma samples were collected from antecubital and uterine veins at the time of cesarean section. The concentrations of sVEGFR-1 and PlGF were determined using specific enzyme-linked immunoassays. The differences of plasma concentrations of sVEGFR-1 and PlGF between uterine and antecubital veins in both groups were compared by paired t-tests.
  
  
  RESULTS
  Patients with preeclampsia had a significantly higher mean plasma concentration of sVEGFR-1 in the uterine vein than in the antecubital vein (uterine vein: mean 13,675 +/- 5,684 pg/ml vs. antecubital vein: mean 10,234 +/- 4,700 pg/ml; paired t-tests, p = 0.04). In contrast, among normal pregnant women at term, there was no significant difference in plasma concentrations of sVEGFR-1 between the uterine and antecubital veins (uterine vein: mean 1,918 +/- 665 pg/ml vs. antecubital vein: mean 1,750 +/- 475 pg/ml; paired t-tests, p = 0.1). The mean plasma concentration of sVEGFR-1, either in the antecubital or uterine vein, was significantly higher in preeclampsia than in normal pregnancy (unpaired t-tests; both p < 0.001). There was no significant difference in the mean plasma concentration of PlGF between the uterine and the antecubital veins in both the preeclamptic (uterine vein, mean +/- SD: 129 +/- 106 pg/ml vs. antecubital vein, mean +/- SD: 82 +/- 43 pg/ml; paired t-tests, p = 0.2) and normal pregnancy groups (uterine vein, mean +/- SD: 331 +/- 254 pg/ml vs. antecubital vein, mean +/- SD: 319 +/- 259 pg/ml; paired t-tests, p = 0.4). The mean plasma concentration of PlGF, either in the uterine or antecubital vein, was lower in preeclampsia than in normal pregnancy (unpaired t-tests; p = 0.008 and 0.02 respectively).
  
  
  CONCLUSIONS
  Plasma concentration of sVEGFR-1 was higher in the uterine vein than in the antecubital vein in women with preeclampsia. This provides evidence supporting the concept that the uterus is a potential source of the excess circulating sVEGFR-1 concentration in preeclamptic women.
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women's Hospital, Detroit, Michigan 48201, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bujold
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Yeon Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Kim
authors.forename: Jimmy
authors.initials: J
authors.lastname: Espinoza
authors.forename: Luís F
authors.initials: LF
authors.lastname: Gonçalves
authors.forename: Samuel
authors.initials: S
authors.lastname: Edwin
authors.forename: Moshe
authors.initials: M
authors.lastname: Mazor
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D004550:Elbow / Q000098:blood supply; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D014599:Uterus / Q000098:blood supply / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1