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

Victoria L Bills , Julia Varet , Ann B Millar , Steven J Harper , Peter W Soothil , David Bates (1)

1 Microvascular Research Laboratories

Pre-eclampsia is a pregnancy related condition characterised by hypertension, proteinuria and endothelial dysfunction. VEGF165b, formed by alternative splicing of vascular endothelial growth factor (VEGF) pre-mRNA inhibits VEGF165 mediated vasodilatation and angiogenesis, but has not been quantified in pregnancy. Enzyme-linked immunoassays (ELISA) were used to measure mean±SEM plasma VEGF165b, soluble endoglin (sEng) and soluble Flt1 (sFlt-1). At 12 weeks gestation the plasma VEGF165b concentration was significantly upregulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group 4.90 ±1.6 ng/ml, p<0.01 Mann-Whitney U test) compared with non-pregnant women (0.40±0.22ng/ml). In contrast, in patients who later developed pre-eclampsia VEGF165b levels were lower than in the normotensive group (0.467 ±0.21 ng/ml) but no greater than non-pregnant women. At term plasma VEGF165b concentrations was greater than normal in both pre-eclamptic (3.75 ±2.24 ng/ml) and normotensive pregnancies (10.6ng/ml±3.84 ng/ml p>0.1 compared with pre-eclampsia). Patients with a lower than median plasma VEGF165b at 12 weeks, had elevated soluble fms-like tyrosine kinase receptor 1 (sFlt-1) and soluble endoglin (sEng) pre-delivery. Concentrations of sFlt-1 (1.20±0.07 ng/ml and 1.27±0.18ng/ml) and sEng (4.4±0.18 vs 4.1±0.5) were similar at 12 weeks gestation in the normotensive and pre-eclamptic groups, respectively. Plasma VEGF165b levels were elevated in pregnancy, but this elevation is delayed in women that subsequently develop pre-eclampsia. Low VEGF165b may therefore be a clinically useful first trimester plasma marker for increased pre-eclampsia risk.

Mots clés: Medicine

Victoria L Bills, Julia Varet, Ann B Millar, Steven J Harper, Peter W Soothil, et al.. Failure to upregulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia. Clinical Science, 2009, 116 (3), pp.265-272. ⟨10.1042/CS20080270⟩. ⟨hal-00479442⟩