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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 11 5555-5563
Copyright © 2003 by The Endocrine Society

Overexpression of the Soluble Vascular Endothelial Growth Factor Receptor in Preeclamptic Patients: Pathophysiological Consequences

Vassilis Tsatsaris, Frederic Goffin, Carine Munaut, Jean-François Brichant, Marie-Rose Pignon, Agnes Noel, Jean-Pierre Schaaps, Dominique Cabrol, Francis Frankenne and Jean-Michel Foidart

Department of Obstetrics and Gynecology (F.G., J.-F.B., J.-P.S., J.-M.F.), Hôpital de la Citadelle, B-4000 Liège, Belgium; Department of Obstetrics and Gynecology (V.T., D.C.), Hôpital Cochin, Maternité Port-Royal, Université Rene Descartes, F-75014 Paris, France; Laboratory of Tumor and Developmental Biology (V.T., F.G., C.M., M.-R.P., A.N., F.F., J.-M.F.), University of Liège, C.R.C.E., Belgium; and Department of Human Embryology (J.-P.S.), University of Liège, Liège, Belgium

Address correspondence and reprint requests to: Jean-Michel Foidart, Department of Obstetrics and Gynecology, Hôpital de la Citadelle, Liège, Belgium. E-mail: jm.foidart{at}ulg.ac.be, or jean.michel.foidart{at}chrcitadelle.be.

Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development.

V.T. and F.G. should be considered as first authors.

This work was supported by a grant from the Fond National pour la Recherche Scientifique (FNRS, Belgium) and a grant from the Collège National des Gynécologues Obstetriciens Français (CNGOF), France.

Abbreviations: CTR, Internal control; HIF, hypoxia-inducible factor; IUGR, intrauterine growth retardation; NRP, neuropilin; PlGF, placental growth factor; sVEGFR-1, soluble form of VEGFR-1; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.




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