title: Microvesicles and pre-eclampsia.
abstract: The maternal syndrome of pre-eclampsia is characterised by an excessive inflammatory response associated with endothelial dysfunction, brought about by the release of multiple factors from the placenta into the maternal circulation. While some of these factors are released as soluble molecules it is now apparent that many of them are associated with syncytiotrophoblast microvesicles and exosomes (collectively termed STBM), which are present in increased amounts in the circulation of women with pre-eclampsia. We have shown that STBM have proinflammatory, anti-endothelial and procoagulant activities in vitro, all of which are features of the maternal syndrome. We propose that the different effects of STBM result from different types of vesicles within the circulation the smaller exosomes being immunoregulatory and the larger microvesicles being proinflammatory, with a shift to the latter in pre-eclampsia. In support of this, we have demonstrated using a novel technique, Nanoparticle Tracking Analysis, that pre-eclampsia STBM are indeed larger than those from normal placentas. Furthermore, the range and types of factors they carry (and hence their functions) may differ in pre-eclampsia, where the syncytiotrophoblast is subjected to oxidative and inflammatory stress. We have carried out proteomic analysis on vesicles prepared from normal and pre-eclampsia placentas by perfusion and have identified differences in the repertoire of molecules they carry. Candidates include immunoregulatory molecules (B7-H1, CD200 and Galectin 1), complement and complement regulatory molecules (C1q, C3, CD55, CD59 and vitronectin), proinflammatory molecules (HSP70, HMGB1, Galectin 3 and Synctin 1), anti-angiogenic molecules (CD49e, CD51, CD26, Flt-1 and endoglin) and procoagulant molecules (tissue factor and phosphatidylserine). Characterising the molecular cargos of the STBM may lead to the discovery of new biomarkers for pre-eclampsia and inform future treatments.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Sargent