title: Protein composition of microparticles shed from human placenta during placental perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia.
abstract: Shedding of syncytiotrophoblast microparticles (MPs) from placenta to maternal blood occurs in normal pregnancy and is enhanced during preeclampsia (PE). The syncytiotrophoblast synthesizes plasminogen activator inhibitors (PAIs) which regulate fibrinolysis, as well as soluble forms of the fms-like tyrosine kinase (sFlt-1) and endoglin, which exert anti-angiogenic actions. An increase in the ratio of PAI-1/PAI-2 and elevated levels of sFlt-1 and sEng in maternal serum are linked to placental damage and maternal endothelial cell dysfunction in PE. The goal of the current study was to determine whether MPs released to maternal perfusate during dual perfusion contain these factors associated with placental pathophysiology in PE. Initially, high levels of alkaline phosphatase activity and Annexin V binding were found in MPs isolated by sequential centrifugation of maternal perfusates at 10,000 and 150,000×g(10 K and 150 K MPs), indicating their plasma membrane origin. ELISA revealed the presence of these factors at the following relative levels: Eng>PAI-2⋙PAI-1>sFlt-1. Based on comparisons of their concentration in perfusates, MPs, and MP-free 150 K supernatants, we determined that MPs constitute a significant portion of Eng released by placenta. Flow cytometric analysis of 10 K MPs supported the levels of expression found by ELISA and indicated that Eng and PAI-2 were almost exclusively localized to the surface of MPs, a site with biological potential. These results indicate that MPs shed from the syncytial surface express factors which may alter the fibrinolytic and angiogenic balance at the maternal-fetal interface and play a role in the pathophysiology of PE.
authors.affiliation: Department of Obstetrics Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven CT, USA. seth.guller@yale.edu
authors.forename: S
authors.initials: S
authors.lastname: Guller
authors.forename: Z
authors.initials: Z
authors.lastname: Tang
authors.forename: Y Y
authors.initials: YY
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Di Santo
authors.forename: R
authors.initials: R
authors.lastname: Sager
authors.forename: H
authors.initials: H
authors.lastname: Schneider
mesh_terms: D055252:Cell-Derived Microparticles / Q000737:chemistry* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008970:Molecular Weight; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010477:Perfusion / Q000379:methods; D010920:Placenta / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011506:Proteins / Q000032:analysis* / Q000378:metabolism; D020543:Proteome / Q000032:analysis
chemical_list: D011506:Proteins; D020543:Proteome