Journal Article

Differential Expression of Vegfr-2 and Its Soluble Form in Preeclampsia

Coulon, Capucine, Goffin, Frédéric, Noël, Agnès, Subtil, Damien, Lorquet, Sophie, Le Goarant, Jeanne, Foidart, Jean-Michel, Munaut, Carine, Chantraine, Frédéric, Tsatsaris, Vassilis, Pequeux, Christel

2012

Overview

Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta. By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas. Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Alternative splicing / Analysis / Angiogenesis / Antigens, CD - blood / Biology / Cancer / Cardiovascular disease / Endoglin / Endothelium / Enzyme-Linked Immunosorbent Assay / Enzymes / Female / France / Gestational age / Gynecology / Human health sciences / Humans / Hypertension / Immunohistochemistry / Kinases / Laboratories / Ligands / Medical research / Medicine / mRNA / Médecine de la reproduction (Gynécologie, andrologie, obstétrique) / Obstetrics / Pathogenesis / Physiology / Placenta / Placenta - metabolism / Plasma levels / Polymerase chain reaction / Postpartum / Pre-eclampsia / Pre-Eclampsia - blood / Preeclampsia / Pregnancy / Receptors, Cell Surface - blood / Reproductive medicine (gynecology, andrology, obstetrics) / Reverse Transcriptase Polymerase Chain Reaction / RNA / Rodents / Sciences de la santé humaine / Statistics, Nonparametric / Vascular endothelial growth factor / Vascular Endothelial Growth Factor Receptor-1 - blood / Vascular Endothelial Growth Factor Receptor-2 - blood / Vascular Endothelial Growth Factor Receptor-2 - metabolism / Vascular endothelial growth factor receptors / Womens health