Plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated prior to the clinical diagnosis of pre-eclampsia

Objective: Accumulating evidence suggests that the balance between vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and their receptors is important for effective vasculogenesis, angiogenesis, and placental development. Recently, the soluble form of VEGFR-1 (sVEGFR-1), an antagonist to VEGF and PlGF, has been implicated in the pathophysiology of pre-eclampsia. Plasma sVEGFR-1 concentration is elevated in pre-eclampsia at the time of clinical diagnosis and correlates with the severity of the disease. The purpose of this study was to determine whether the concentrations of sVEGFR-1 in plasma of pre-eclamptic patients change prior to the clinical manifestations of the disease. Methods: A longitudinal case-control study was conducted in normal pregnant women (n = 44) and patients with pre-eclampsia (n = 44). Blood sampling was performed at six intervals: (1) 7-16 weeks; (2) 16-24 weeks; (3) 24-28 weeks; (4) 28-32 weeks; (5) 32-36 weeks; and (6) more than 37 weeks of gestation. To examine the relationship between plasma sVEGFR-1 concentration and interval to clinical diagnosis of pre-eclampsia, plasma samples of pre-eclamptic patients at different gestational ages were stratified according to the interval from blood sampling to clinical development of the disease into five groups: (1) at clinical manifestation; (2) 2-5 weeks; (3) 6-10 weeks; (4) 11-16 weeks; and (5) 17-25 weeks before clinical manifestations. Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay. Parametric statistics and repeated measure procedures were used for the analysis. Results: The mean plasma sVEGFR-1 concentration in pre-eclamptic patients before the clinical manifestation of the disease was significantly higher than in normal pregnant women at 24-28, 28-32, and 32-37 weeks of gestation (p = 0.02, p < 0.001, and p < 0.001, respectively). In contrast, no significant differences in the mean plasma sVEGFR-1 concentration between patients with pre-eclampsia and normal pregnant women were observed both at 7-16 weeks and 16-24 weeks of gestation (p = 0.1 and p = 0.9). Similarly, the mean plasma sVEGFR-1 concentration was significantly higher in pre-eclamptic patients than in normal pregnant women at clinical manifestation, at 2-5 weeks (mean 3.8 weeks), and at 6-10 weeks (mean 8.2 weeks) prior to the development of clinical pre-eclampsia (p < 0.001, p < 0.001, and p = 0.002, respectively). Among patients with early-onset pre-eclampsia (defi