title: Effects of normal and high circulating concentrations of activin A on vascular endothelial cell functions and vasoactive factor production.
abstract: OBJECTIVE
  Activin A, a TGFβ family member, circulates in the maternal blood at increasing concentrations throughout gestation during a healthy pregnancy. The circulating concentration of activin A is further increased in pre-eclampsia (PE), a hypertensive disorder of pregnancy that is marked by systemic maternal vascular endothelial cell dysfunction. The effect of increasing activin A concentrations on the maternal vascular endothelium is unknown. The study aim was to investigate the effect of physiological and pathological activin A concentrations observed in normotensive and PE pregnancies respectively, on vascular endothelial cell function.
  
  
  RESULTS
  Immunostaining demonstrated the presence of the activin A receptor, ACVR2A, in SGHEC-7 cells used to model the vascular endothelium. SGHEC-7 cells were treated with activin A concentrations representative of concentrations throughout gestation in normotensive (0-10ng/ml) and PE (50ng/ml) pregnancies. xCELLigence functional assays revealed that normotensive activin A concentrations increased SGHEC-7 proliferation and migration, which was inhibited by PE concentrations. Additionally, fluorescence based assays showed that PE concentrations increased endothelial permeability. None of the tested activin A concentrations affected cell apoptosis. PE concentrations also resulted in an imbalance of the vasoactive factors eNOS, PTGIS and EDN1, as determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays.
  
  
  CONCLUSIONS
  Compared with normotensive activin A concentrations, the higher PE activin A concentrations resulted in abnormal endothelial functions, which may contribute to the systemic maternal vascular endothelial cell dysfunction observed in the disorder.
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre and The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia. Electronic address: ejyong@student.unimelb.edu.au.
authors.forename: Hannah E J
authors.initials: HE
authors.lastname: Yong
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre and The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia.
authors.forename: Padma
authors.initials: P
authors.lastname: Murthi
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre and The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia.
authors.forename: May H
authors.initials: MH
authors.lastname: Wong
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre and The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia.
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
authors.affiliation: Institute of Cardiovascular and Cell Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Cartwright
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre and The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia.
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre and The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia.
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Keogh
mesh_terms: D030301:Activin Receptors, Type II / Q000097:blood; D028341:Activins / Q000097:blood*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011247:Pregnancy; D012680:Sensitivity and Specificity; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C422405:activin A; D028341:Activins; D040281:Vascular Endothelial Growth Factor Receptor-1; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A
keywords: Activin A; Anti-angiogenic; Endothelial dysfunction; Pre-eclampsia