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

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

Séroconversion toxoplasmique périconceptionnelle (bilan de la prise en charge obstétricale et néonatale de 1996 à 2005 à l'Hôpital Jeanne de Flandre à propos de 79 cas)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Representative immunolocalization of VEGFR-1 (A–B), VEGFR-2 (C, D and E) and CD31 (F).

<p>Placental villi from a normal pregnant women (A, C, E and F) and from a preeclamptic women (B–D): VEGFR-1 is expressed in the cytotrophoblasts, syncytiotrophoblasts (arrow) and also in some endothelial cells (white arrow head). VEGFR-2 is mainly localized in vascular endothelial cells (arrows) in placentas of both groups as identified by serial section immunostaining with CD31.</p

Maternal plasma analysis.

<p><b>A</b>: Western blot analysis of VEGFR-1 and VEGFR-2 from gestational age-matched normal pregnant women (NP, 1–5) and preeclamptic women (PE, 6–10). <b>B</b>: Maternal plasma concentration of VEGFR1, VEGFR2 and Eng (mean±SE, pg/ml) at inclusion (Incl), delivery (day 0, D 0) and during post partum (day 1 to day 5, D 1 to D 5). PE: severe preeclampsia (plain line), NP: normal pregnancies (dashed line).</p

Placental VEGFR-2 and sVEGFR-2 relative mRNA levels.

<p><b>A</b>: Schematic representation of pre-mRNA exon-intron structure of VEGFR-2 (central shadowed box not at scale) with primers used to discriminate membrane bound VEGFR-2 mRNA (upper box, exon 13-exon 16; 634 bp) and soluble VEGFR-2 mRNA (lower box, exon 13-intron 13; 278 bp). <b>B</b>: Relative mRNA levels are expressed as arbitrary units (A.U.). NP: normal pregnancies, PE: severe preeclampsia. **<i>P</i><0.001 compared to NP group; ns: non-significant compared to NP group.</p

Clinical characteristics.

<p>NP: normal pregnancies; PE: severe preeclampsia; NA: not applicable; BMI: body mass index.</p>*<p><i>P</i><0.05 and.</p>**<p><i>P</i><0.001 compared to NP group.</p

Placental VEGFR-1, sVEGFR-1 and Eng relative mRNA levels.

<p>Relative mRNA levels are expressed as arbitrary units (A.U.). NP: normal pregnancies, PE: severe preeclampsia. **<i>P</i><0.001 compared to NP group; ns: non-significant compared to NP group.</p

Maternal plasma concentration of VEGFR-1, VEGFR-2 and Eng in normal gestational age matched to PE delivery and preeclamptic pregnancies (median and quartiles (25^th–75^th centile), ng/ml).

<p>Maternal plasma concentration of VEGFR-1, VEGFR-2 and Eng in normal gestational age matched to PE delivery and preeclamptic pregnancies (median and quartiles (25^th–75^th centile), ng/ml).</p