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Reproductive Sciences
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Circulating Platelet-derived and Placenta-derived Microparticles Expose Flt-1 in Preeclampsia

Christine A. R. Lok, MD, PhD

Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, Netherlands, c.a.lok@ amc.uva.nl

Anita N. Böing, Ing

Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry, Academic Medical Center, Amsterdam, Netherlands

Ian L. Sargent, PhD

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, The Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom

Suren R. Sooranna, PhD

Department of Maternal Fetal Medicine, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, United Kingdom

Joris A. M. van der Post, MD, PhD

Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, Netherlands

Rienk Nieuwland, PhD

Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry, Academic Medical Center, Amsterdam, Netherlands

Augueste Sturk, PhD

Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry, Academic Medical Center, Amsterdam, Netherlands

Background. Flt-1 is secreted by various cells and elevated concentrations are present in preeclampsia affecting vascular function. Microparticles from these cells may expose Flt-1. We evaluated whether Flt-1 is microparticle-associated in preeclampsia, and established the origin of Flt-1-exposing microparticles. Methods. The concentration of Flt-1 was measured in samples from preeclamptic patients, pregnant and nonpregnant women by enzyme-linked immunosorbent assay. Microparticles were analyzed by flow cytometry. Western blot determined the different forms of Flt-1. Results. Noncell bound Flt-1 was elevated in preeclampsia compared to controls. A fraction (5%) was associated with microparticles in preeclampsia. Flt-1-exposing microparticles were increased in preeclampsia compared to normotensive pregnancy (p = 0.02). Full-length Flt-1, was identified in microparticles of platelet and placental origin. Conclusion. Full-length Flt-1 is associated with platelet and placenta-derived microparticles. Possibly, the presentation of Flt-1 on the membrane of a microparticle might alter its function, particularly if it acts in synergism with other exposed vasoactive molecules.

Key Words: Flt-1 • microparticles • preeclampsia • sFlt-1 • VEGF.

This version was published on December 1, 2008

Reproductive Sciences, Vol. 15, No. 10, 1002-1010 (2008)
DOI: 10.1177/1933719108324133
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