Endothelial tie receptor antigen in maternal and cord blood of healthy and preeclamptic subjects

Abstract
Objective: To measure the vascular endothelial receptor tyrosine kinase Tie, essential in the process of angiogenesis, in blood from healthy and preeclamptic pregnant women, in umbilical cord blood from both, and in blood from nonpregnant women. Methods: A total of 143 women participated in four arms of the study. Blood samples were collected from 54 healthy nonlaboring pregnant women (gestational weeks 14–41). Samples were collected immediately prepartum and postpartum from another 40 healthy women (15 delivered vaginally and 25 by cesarean) and 15 preeclamptic women (all delivered by cesarean). Arterial and venous cord samples were collected, when possible, from infants born by cesarean. Single blood samples were drawn from 34 nonpregnant controls. Of these, weekly samples from 11 were drawn during one menstrual cycle. A time-resolved fluoroimmunoassay was developed for the detection of the soluble extracellular domain of Tie. Results: Maternal serum Tie levels decreased with advancing gestational age after 26 weeks (r = .6, P < .001). They were significantly higher in healthy women at term (median 233 ng/mL, range 152–414 ng/mL) compared with nonpregnant controls (median 173 ng/mL, range 107–333 ng/mL, P < .001) or with preeclamptic women at term (median 152 ng/mL, range 90–372 ng/mL, P < .05). This difference between healthy and preeclamptic women persisted on the first postpartum day (median 221 ng/mL, range 128–343 and median 152 ng/mL, range 90–372 ng/mL, respectively, P < .05). The highest levels of serum Tie receptor were observed in umbilical arterial and venous blood (median 240 ng/mL, range 174–474 ng/mL and median 340 ng/mL, range 245–690 ng/mL, respectively). In nonpregnant women, serum Tie levels did not vary with menstrual cycle. Conclusion: The high levels of the extracellular domain of Tie in healthy term maternal and cord blood may indicate a role for Tie in the vascular development of human fetuses and placentas.