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 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.
Bills
Victoria L
VL
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol BS2 8EJ, U.K.
Varet
Julia
J
Millar
Ann
A
Harper
Steven J
SJ
Soothill
Peter W
PW
Bates
David O
DO
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005865:Gestational Age; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008423:Maternal Age; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A