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This version published online on October 29, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-0715
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Submitted on March 31, 2009
Accepted on October 13, 2009

Maternal Serum Angiopoietin-1 and -2 and Tie-2 in Early Pregnancy Ending in Preeclampsia or Intrauterine Growth Retardation

Elina Leinonen*, Katja-Anneli Wathén, Henrik Alfthan, Olavi Ylikorkala, Sture Andersson, Ulf-Håkan Stenman, and Piia Vuorela

Departments of Obstetrics and Gynecology (E.L., K.-A.W., O.Y., P.V.), Clinical Chemistry (H.A., U.-H.S.), and Pediatrics (S.A.), Helsinki University Central Hospital, Biomedicum, Helsinki 00029 HUS, Finland

* To whom correspondence should be addressed. E-mail: elina.a.leinonen{at}helsinki.fi.

Context: The antiangiogenic growth factor angiopoietin-2 (Ang-2) antagonizes, whereas angiopoietin-1 (Ang-1) activates the endothelial cell-specific tyrosine kinase receptor-2 (Tie-2). In preeclampsia, circulating concentrations of Ang-1 are increased and those of Ang-2 and Tie-2 are decreased.

Objective: We wanted to study whether maternal serum concentrations of Ang-1, Ang-2, and Tie-2 are altered at gestational wk 12–15 or 16–20 in women with subsequent preeclampsia or intrauterine growth retardation (IUGR).

Design: This was a case-control study.

Setting: The study was conducted in Helsinki University Central Hospital, a tertiary referral center.

Patients: This study comprised 124 pregnant women, of whom 49 developed preeclampsia and 16 gave birth to infants with IUGR, and 59 healthy women served as controls.

Main Outcome Measures: Serum concentrations of Ang-1, Ang-2, and Tie-2 were assessed by ELISA. Data were combined with our earlier data on soluble VEGF receptor (sVEGFR)-1.

Results: At gestational wk 12–15, the median concentrations of Ang-1, Ang-2, or Tie-2 were all similar between the study groups. At 16–20 wk, Ang-2 concentrations were higher in women with subsequent preeclampsia [25.0 ng/ml, 19.3–39.5 ng/ml; median, interquartile range (IQR)] than in the controls (17.7 ng/ml, 10.8–27.4 ng/ml, P = 0.006). The odds ratio of high Ang-2 concentrations for subsequent preeclampsia was 4.2 (95% confidence interval 1.4–12.6; P = 0.011) and high Ang-2 combined with high sVEGFR-1, 6.4 (95% confidence interval 2.2–18.7; P = 0.001).

Conclusion: Maternal serum Ang-2 concentrations are increased prior to preeclampsia. High concentrations of both Ang-2 and sVEGFR-1 indicate subsequent disease.







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