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Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1), by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women.

Publication ,  Journal Article
Rajakumar, A; Michael, HM; Rajakumar, PA; Shibata, E; Hubel, CA; Karumanchi, SA; Thadhani, R; Wolf, M; Harger, G; Markovic, N
Published in: Placenta
August 2005

The soluble VEGF receptor, sFlt-1 (otherwise referred to as sVEGFR-1), has been implicated in the pathogenesis of preeclampsia. The preeclamptic placenta has been previously demonstrated to produce high levels of the soluble VEGF receptor. Here we tested the hypothesis that peripheral blood mononuclear cells (PBMCs) may also represent an additional source for circulating sFlt-1 during normal and preeclamptic pregnancies. We first demonstrate that preeclamptic placentae show five-fold increased Flt-1 and sFlt-1 mRNA levels. We also show that the Flt-1 and sFlt-1 levels are eight-fold higher in preeclamptic placentae if we collect biopsies without rinsing them in saline to remove excess blood. Cultured villous explants from women with preeclampsia failed to show the increased amount of Flt-1 and sFlt-1 mRNA that was observed in the placental biopsies of normal pregnancy and preeclampsia. Under normoxic conditions the Flt-1 and sFlt-1 mRNA levels in the explants were 3.11+/-0.6 fold in normal pregnancy and 3.6+/-0.4 fold in women with preeclampsia (p = NS by ANOVA). However, the same villous explants showed hypoxic induction of Flt-1 mRNA (NP 3.96+/-0.4 fold, p = NS and PE 5.24+/-0.6 fold, p < 0.05 by ANOVA). We analyzed Flt-1 and sFlt-1 protein levels in the peripheral blood mononuclear cells (PBMCs) to analyze the possibility of an extra-placental sFlt-1 source. Our results indicate that PBMCs of pregnant women are capable of expressing variable amounts of Flt-1 proteins. PBMCs from pregnant women exposed to hypoxia show up-regulation of HIF-1alpha and Flt-1 proteins. PBMCs obtained from women with preeclampsia (n = 9) produced significantly higher amounts of sFlt-1 under normal tissue culture conditions (104.6+/-14.3 pg/ml vs. 46.23+/-5.03 pg/ml, p < 0.05 by ANOVA) and much higher concentrations under hypoxia (196.74+/-26.3pg/ml vs. 83.3+/-13.6pg/ml, p < 0.05 by ANOVA) than PBMCs from normal pregnant women (n = 11). Moreover, analysis of PBMCs from a different group of women with a history of preeclampsia showed persistent abnormality of Flt-1 women one year post-partum. The present study indicates that Flt-1 dysregulation in PBMCs of pregnant women resulting in over-expression of sFlt-1 could be an additional (extra-placental) source of sFlt-1 that contributes to the pathogenesis of preeclampsia.

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Published In

Placenta

DOI

ISSN

0143-4004

Publication Date

August 2005

Volume

26

Issue

7

Start / End Page

563 / 573

Location

Netherlands

Related Subject Headings

  • Vascular Endothelial Growth Factor Receptor-1
  • Up-Regulation
  • Transcription Factors
  • RNA, Messenger
  • Pregnancy
  • Pre-Eclampsia
  • Placenta
  • Obstetrics & Reproductive Medicine
  • Nuclear Proteins
  • Leukocytes, Mononuclear
 

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Rajakumar, A., Michael, H. M., Rajakumar, P. A., Shibata, E., Hubel, C. A., Karumanchi, S. A., … Markovic, N. (2005). Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1), by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women. Placenta, 26(7), 563–573. https://doi.org/10.1016/j.placenta.2004.09.001
Rajakumar, A., H. M. Michael, P. A. Rajakumar, E. Shibata, C. A. Hubel, S Ananth Karumanchi, R. Thadhani, M. Wolf, G. Harger, and N. Markovic. “Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1), by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women.Placenta 26, no. 7 (August 2005): 563–73. https://doi.org/10.1016/j.placenta.2004.09.001.
Rajakumar A, Michael HM, Rajakumar PA, Shibata E, Hubel CA, Karumanchi SA, Thadhani R, Wolf M, Harger G, Markovic N. Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1), by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women. Placenta. 2005 Aug;26(7):563–573.
Journal cover image

Published In

Placenta

DOI

ISSN

0143-4004

Publication Date

August 2005

Volume

26

Issue

7

Start / End Page

563 / 573

Location

Netherlands

Related Subject Headings

  • Vascular Endothelial Growth Factor Receptor-1
  • Up-Regulation
  • Transcription Factors
  • RNA, Messenger
  • Pregnancy
  • Pre-Eclampsia
  • Placenta
  • Obstetrics & Reproductive Medicine
  • Nuclear Proteins
  • Leukocytes, Mononuclear