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

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 sFIt-I (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 nonpregnant women. At term, plasma VEGF(165)b concentrations were greater than normal in both preeclamptic (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 sFIt-I and sEng pre-delivery. Concentrations of sFIt-I (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.