Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia

Clin Sci (Lond). 2009 Feb;116(3):265-72. doi: 10.1042/CS20080270.


Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF(165)b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF(165)-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means+/-S.E.M. plasma VEGF(165)b, sEng (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks of gestation, the plasma VEGF(165)b concentration was significantly up-regulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group, 4.90+/-1.6 ng/ml; P<0.01, as determined using a Mann-Whitney U test) compared with non-pregnant women (0.40+/-0.22 ng/ml). In contrast, in patients who later developed pre-eclampsia, VEGF(165)b levels were lower than in the normotensive group (0.467+/-0.209 ng/ml), but were no greater than non-pregnant women. At term, plasma VEGF(165)b concentrations were greater than normal in both pre-eclamptic (3.75+/-2.24 ng/ml) and normotensive (10.58 ng/ml+/-3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with a lower than median plasma VEGF(165)b at 12 weeks had elevated sFlt-1 and sEng pre-delivery. Concentrations of sFlt-1 (1.20+/-0.07 and 1.27+/-0.18 ng/ml) and sEng (4.4+/-0.18 and 4.1+/-0.5 ng/ml) were similar at 12 weeks of gestation in the normotensive and pre-eclamptic groups respectively. Plasma VEGF(165)b levels were elevated in pregnancy, but this increase is delayed in women that subsequently develop pre-eclampsia. In conclusion, low VEGF(165)b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / blood
  • Biomarkers / blood
  • Endoglin
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Gestational Age
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Maternal Age
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis*
  • Pregnancy
  • Pregnancy Proteins / blood*
  • Prognosis
  • Receptors, Cell Surface / blood
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / blood*


  • Antigens, CD
  • Biomarkers
  • ENG protein, human
  • Endoglin
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Pregnancy Proteins
  • Receptors, Cell Surface
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A