Maternal serum angiopoietin-1 and -2 and tie-2 in early pregnancy ending in preeclampsia or intrauterine growth retardation.

Abstract

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. 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). This was a case-control study. The study was conducted in Helsinki University Central Hospital, a tertiary referral center. 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. 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. 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). Maternal serum Ang-2 concentrations are increased prior to preeclampsia. High concentrations of both Ang-2 and sVEGFR-1 indicate subsequent disease.