Vascular pool of releasable soluble VEGF receptor-1 (sFLT1) in women with previous preeclampsia and uncomplicated pregnancy.

CONTEXT: Research examining the source of excess soluble fms-like tyrosine kinase 1 (sFLT1) in preeclampsia has focused on the placenta. The potential contribution of the releasable store of sFLT1 in the systemic vasculature is unknown. OBJECTIVE: We asked whether the nonplacental releasable store of sFLT1 is larger in women with previous preeclampsia than in women with a previous uncomplicated pregnancy. DESIGN: We administered heparin to nulligravid women and to women with previous preeclampsia or a previous uncomplicated pregnancy. We compared post-heparin sFLT1 concentrations with those observed in uncomplicated pregnancy and preeclampsia. SETTING: The study was performed at Magee-Womens Hospital. PATIENTS: Participants included nulligravidas (n = 8), women 6-24 months postpartum (previous uncomplicated pregnancy, n = 16; previous preeclampsia, n = 15), and pregnant women (uncomplicated pregnancy, n = 30; preeclampsia, n = 25). INTERVENTION: Nonpregnant women received an unfractionated heparin bolus. MAIN OUTCOME MEASURES: Pre- and post-heparin plasma sFLT1, placental growth factor, and vascular endothelial growth factor were measured. RESULTS: In nonpregnant women, heparin increased plasma sFLT1 by 250-fold (P < .01), increased placental growth factor by 7-fold (P < .01), and decreased free vascular endothelial growth factor (P < .01). These changes did not differ between nulligravidas, women with previous preeclampsia, and women with a previous uncomplicated pregnancy. Post-heparin sFLT1 in nonpregnant women was higher than sFLT1 in uncomplicated pregnancy, but lower than sFLT1 in preeclampsia. Baseline and post-heparin sFLT1 were positively correlated (r(2) = 0.19; P < .01). Heparin increased the concentration of the 100-kDa sFLT1 isoform. Adding heparin to whole blood or plasma did not increase sFLT1. CONCLUSIONS: Nonpregnant women have a significant vascular store of releasable sFLT1. The size of this store does not differ between women with previous preeclampsia vs women with previous uncomplicated pregnancy.