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


METHODS
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 (<or=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).


CONCLUSIONS
Patients with preeclampsia and those with SGA fetuses have lower median plasma concentrations of soluble Tie-2 than women with normal pregnancies.
Gotsch
Francesca
F
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, USA. prbchiefstaff@med.wayne.edu
Romero
Roberto
R
Kusanovic
Juan Pedro
JP
Chaiworapongsa
Tinnakorn
T
Dombrowski
Michael
M
Erez
Offer
O
Than
Nandor Gabor
NG
Mazaki-Tovi
Shali
S
Mittal
Pooja
P
Espinoza
Jimmy
J
Hassan
Sonia S
SS
D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D042787:Receptor, TIE-2 / Q000097:blood*
D015415:Biomarkers; D042787:Receptor, TIE-2