Preeclampsia and small-for-gestational age are associated with decreased concentrations of a factor involved in angiogenesis: Soluble Tie-2

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Abstract
Objective. An anti-angiogenic state has been described in patients with preeclampsia, small-for-gestational age (SGA) fetuses and fetal death, and changes in the concentration of circulating angiogenic and anti-angiogenic factors can precede the clinical recognition of preeclampsia and SGA by several weeks. Gene deletion studies demonstrate that a selective group of endothelial growth factors are required for vascular development, including members of the vascular endothelial growth factor (VEGF) family, as well as angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), both ligands for the tyrosine kinase endothelial cell receptor Tie-2. These angiogenic factors have been proposed to promote angiogenesis in a coordinated and complementary fashion. Soluble Tie-2 (sTie-2) is the soluble form of the Tie-2 receptor, which is detectable in biological fluids. The purpose of this study was to determine whether patients with preeclampsia and mothers who deliver a SGA neonate have changes in the plasma concentrations of sTie-2. Study design. This cross-sectional study included patients in the following groups: (1) non-pregnant women (n = 40), (2) women with normal pregnancies (n = 135), (3) patients with preeclampsia (n = 112), and (4) patients who delivered an SGA neonate (n = 53). Maternal plasma concentrations of sTie-2 were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis. Results. (1) The median maternal plasma concentration of sTie-2 was lower in normal pregnant women than in non-pregnant women [median 16.0 ng/mL (range 5.0–71.6) vs. median 20.7 ng/mL (range 10.8–52.4), respectively; p = 0.01)). (2) Plasma sTie-2 concentrations in normal pregnancy changed significantly as a function of gestational age. (3) Patients with preeclampsia and those who delivered SGA neonates had a lower median maternal plasma concentration of sTie-2 than those with a normal pregnancy [preeclampsia: median 14.9 ng/mL (range 4.9–67.3); SGA: median 10.9 ng/mL (range 5.1–29.1); normal pregnancy: median 16.0 ng/mL (range 5.0–71.6); p = 0.048 and p < 0.001, respectively]. (4) Patients with SGA neonates had a lower median plasma concentration of sTie-2 than that of those with preeclampsia [median 10.9 ng/mL (range 5.1–29.1) vs. median 14.9 ng/mL (range 4.9–67.3), respectively; p < 0.001]. (5) Patients with early-onset preeclampsia (≤34 weeks) had lower concentrations of sTie-2 than women with late-onset preeclampsia (>34 weeks) median of delta values: −0.13 ng/mL (range −0.47–0.58) vs. median of delta values: −0.09 ng/mL (range: −0.60–0.58), respectively; p = 0.043]. In contrast, there were no significant differences in the maternal plasma sTie-2 concentration between women with severe and mild preeclampsia (p = 0.6). Conclusion. Patients with preeclampsia and those with SGA fetuses have lower median plasma concentrations of soluble Tie-2 than women with normal pregnancies.