title: Syncytiotrophoblast Extracellular Vesicles from Pre-Eclampsia Placentas Differentially Affect Platelet Function.
abstract: Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Dionne S
authors.initials: DS
authors.lastname: Tannetta
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hunt
authors.affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, Berkshire, United Kingdom.
authors.forename: Chris I
authors.initials: CI
authors.lastname: Jones
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Naomi
authors.initials: N
authors.lastname: Davidson
authors.affiliation: School of Physiology and Pharmacology, University of Bristol, Medical Sciences Building, University Walk, Bristol, United Kingdom.
authors.forename: Carmen H
authors.initials: CH
authors.lastname: Coxon
authors.affiliation: Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Ferguson
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Redman
authors.affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, Berkshire, United Kingdom.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gibbins
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Ian L
authors.initials: IL
authors.lastname: Sargent
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Tucker
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology*; D016022:Case-Control Studies; D000067128:Extracellular Vesicles / Q000473:pathology / Q000502:physiology; D005260:Female; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010920:Placenta / Q000473:pathology / Q000503:physiopathology*; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D011225:Pre-Eclampsia / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D013927:Thrombosis / Q000209:etiology; D014327:Trophoblasts / Q000473:pathology / Q000502:physiology*
chemical_list: D001241:Aspirin