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

Abstract

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.

• Authors: Tracey L Weissgerber, Augustine Rajakumar, Ashley C Myerski, Lia R Edmunds, Robert W Powers, James M Roberts, Robin E Gandley, Carl A Hubel
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 99 Issue 3 Pg. 978-87 (Mar 2014) ISSN: 1945-7197 [Electronic] United States
• PMID: 24423299 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Heparin
• FLT1 protein, human
• Vascular Endothelial Growth Factor Receptor-1

Topics

• Adult
• Female
• Gravidity
• Heparin (administration & dosage)
• Humans
• Parity
• Postpartum Period (blood, drug effects)
• Pre-Eclampsia (blood, prevention & control)
• Pregnancy (blood)
• Reproductive History
• Vascular Endothelial Growth Factor Receptor-1 (blood)
• Young Adult