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

Tinnakorn Chaiworapongsa, Roberto Romero, Yeon Mee Kim, Gi Jin Kim, Mi Ran Kim, Jimmy Espinoza, Emmanuel Bujold, Luis Gonçalves, Ricardo Gomez, Samuel Edwin, Moshe Mazor

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    314 Scopus citations

    Abstract

    Objective: Accumulating evidence suggests that the balance between vascular endothelial growth factor (VEGF), placental growth factor (PIGF), 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 PIGF, 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 (defined as gestational age of 34 weeks or less), the mean plasma sVEGFR-1 concentration was significantly higher in pre-eclampsia (before clinical diagnosis) than in normal pregnant women at 24-28 (mean 26.4) weeks of gestation (p = 0.008). In contrast, among patients with the late-onset disease (defined as gestational age of more than 34 weeks), plasma sVEGFR-1 concentration in pre-clinical pre-eclampsia was significantly higher than in normal pregnant women at 28-32 (mean 30.2) weeks of gestation (p < 0.001). Conclusions: Plasma sVEGFR-1 concentration is elevated in pre-eclampsia prior to the clinical diagnosis of the disease. This elevation began 6-10 weeks prior to the clinical manifestations, and the increase was more pronounced at 2-5 weeks before the diagnosis, as well as at clinical presentation. Furthermore, in early-onset pre-eclampsia, plasma concentration of sVEGFR-1 is elevated earlier than the late-onset disease.

    Original languageEnglish
    Pages (from-to)3-18
    Number of pages16
    JournalJournal of Maternal-Fetal and Neonatal Medicine
    Volume17
    Issue number1
    DOIs
    StatePublished - 1 Jan 2005

    Keywords

    • Early onset
    • Late onset
    • Longitudinal study
    • PIGF
    • Plasma-soluble vascular endothelial growth factor 1
    • Pre-eclampsia
    • VEGF

    ASJC Scopus subject areas

    • Pediatrics, Perinatology, and Child Health
    • Obstetrics and Gynecology

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