45 On the origin and disappearance of sFlt-1 and PlGF in preeclampsia

Abstract

Background The pro-angiogenic placental growth factor (PlGF) and the anti-angiogenic, PlGF-sequestering soluble receptor (sFlt-1) are both released from the placenta into the maternal circulation during pregnancy. In preeclampsia (PE), the balance shifts towards sFlt-1, resulting in an elevated sFlt-1/PlGF ratio. It is currently unknown how fast these proteins disappear after delivery, and to what degree extraplacental sources contribute to their levels. Objective To investigate the changes in sFlt-1 and PlGF levels in PE women after delivery. Methods Serum sFlt-1 and PlGF levels were measured in 23 women aged 20–41 years with a median duration of labor of 27 weeks (range 24–32 weeks) using the automated Elecsys system. The women were randomly chosen from a big PE cohort, and samples were taken both before and after delivery. Concentrations after delivery were expressed as a percentage of the concentration in the last sample that was taken during pregnancy. Results Median sFlt-1 and PlGF concentrations at the final stage of pregnancy were 11007 (3593–85000) and 26 (6–237) pg/mL, respectively, and the ratio was 544 (83–1034). SFlt-1 decreased with a half-life of 1.2 ± 0.4 days, and then stabilized at levels corresponding with 0.3 ± 0.2% of the level during pregnancy. PlGF decreased with a half-life of 4.8 ± 1.6 and then stabilized at levels corresponding with 14.7 ± 4.1% of the level during pregnancy. Changes in the ratio paralleled those in sFlt-1. Conclusions sFlt-1, but not PlGF, almost exclusively ( > 99%) originates in the placenta, and disappears more rapidly after delivery, thus allowing a quick normalization of the sFlt-1/PlGF ratio. Future studies should address the kinetics of these parameters in women with an uncomplicated pregnancy, and investigate whether sFlt-1 levels, despite a massive reduction, remain elevated in PE women vs. healthy pregnant women after delivery.