Tannetta, DS;
Dragovic, RA;
Gardiner, C;
Redman, CW;
Sargent, IL;
(2013)
Characterisation of syncytiotrophoblast vesicles in normal pregnancy and pre-eclampsia: expression of Flt-1 and endoglin.
PLoS One
, 8
(2)
, Article e56754. 10.1371/journal.pone.0056754.
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Abstract
BACKGROUND: The placental syncytiotrophoblast releases micro and nanovesicles (STBM), into the maternal circulation in normal pregnancy and in increased amounts in pre-eclampsia (PE), which have proinflammatory and antiangiogenic activity and are implicated in PE pathophysiology. Better characterisation of STBM is essential to understand their role in PE. METHODS AND RESULTS: STBM prepared by placental lobe dual perfusion (pSTBM) and mechanical disruption (mSTBM) were analysed by four colour flow cytometry (4CFC), nanoparticle tracking analysis (NTA) and Western blotting to determine vesicle size, purity and Flt-1 and endoglin (Eng) expression. Biological activity of STBM associated Flt-1 and endoglin was assessed by the ability of VEGF, PlGF and TGFβ to bind to mSTBM and inhibit mSTBM induced endothelial monolayer disruption. STBM content was consistently high (~87-95%) across the different preparations. However, surface antigen intensities differed, with significantly lower placental alkaline phosphatase (P<0.05) and Eng (P<0.05) expression on mSTBM, and Flt-1 (P<0.05) expression on pSTBM. For PE placenta derived preparations, pSTBM contained lower Eng positive STBM (P<0.05) and mSTBM Eng expression was increased (P<0.05). Western blotting revealed increased Flt-1/sFlt-1 (P<0.02) and decreased placental alkaline phosphatase (P = 0.0002) content of PE placenta pSTBM. Using NTA, perfused PE placentas released significantly larger MV (P<0.001). Finally, VEGF, PlGF and TGFβ bound to mSTBM at physiologically relevant concentrations and inhibited mSTBM induced endothelial disruption (P<0.05-P<0.001). CONCLUSIONS: This study has found differences in physical and antigenic characteristics of normal and PE placenta STBM preparations produced by placental perfusion or mechanical disruption. We have also demonstrated that large quantities of biologically active STBM associated endoglin and Flt-1/sFlt-1 could contribute to the increased circulating levels measured in PE patients and add to the perturbation of the maternal vascular endothelium, normally attributed to non-membrane bound sFlt-1 and sEndoglin.
| Type: | Article |
|---|---|
| Title: | Characterisation of syncytiotrophoblast vesicles in normal pregnancy and pre-eclampsia: expression of Flt-1 and endoglin. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0056754 |
| Publisher version: | https://doi.org/10.1371/journal.pone.0056754 |
| Language: | English |
| Additional information: | © 2013 Tannetta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Adult, Antigens, CD, Endoglin, Endothelium, Vascular, Female, Gene Expression Regulation, Humans, Phosphorylation, Placenta, Pre-Eclampsia, Pregnancy, Protein Binding, Receptors, Cell Surface, Signal Transduction, Trophoblasts, Vascular Endothelial Growth Factor Receptor-1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1468521 |
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