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Merck

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

The Journal of clinical endocrinology and metabolism (2014-01-16)
Tracey L Weissgerber, Augustine Rajakumar, Ashley C Myerski, Lia R Edmunds, Robert W Powers, James M Roberts, Robin E Gandley, Carl A Hubel
RESUMEN

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. We asked whether the nonplacental releasable store of sFLT1 is larger in women with previous preeclampsia than in women with a previous uncomplicated pregnancy. 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. The study was performed at Magee-Womens Hospital. 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). Nonpregnant women received an unfractionated heparin bolus. Pre- and post-heparin plasma sFLT1, placental growth factor, and vascular endothelial growth factor were measured. 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. 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.