Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences.
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.
Tsatsaris
Vassilis
V
Department of Obstetrics and Gynecology, Hôpital de la Citadelle, B-4000 Liège, Belgium.
Goffin
Frederic
F
Munaut
Carine
C
Brichant
Jean-François
JF
Pignon
Marie-Rose
MR
Noel
Agnes
A
Schaaps
Jean-Pierre
JP
Cabrol
Dominique
D
Frankenne
Francis
F
Foidart
Jean-Michel
JM
D000328:Adult; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000503:physiopathology; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012995:Solubility; D014599:Uterus / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood / Q000235:genetics
C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2