title: Role of activin A in the pathogenesis of endothelial cell dysfunction in preeclampsia.
abstract: Circulating markers for endothelial activation such as endothelin-1 (ET-1), ICAM-1 and VCAM-1 are elevated in women with preeclampsia. Using human umbilical vein endothelial cells (HUVECs) as an in vitro model of the maternal vasculature, we show that activin A and preeclamptic serum upregulate ET-1, ICAM-1, and VCAM-1 in HUVECs. Further, we show that follistatin, a specific binding protein for activin, mitigates the upregulation of ET-1, ICAM-1 and VCAM-1 in HUVECs exposed to either activin A or preeclamptic serum. These data are consistent with activin A contributing to the pathophysiology of preeclampsia and suggest that therapies targeting activin signalling are worth exploring.
authors.affiliation: Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia; The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia; Monash Women's Services, Monash Health, Clayton, VIC 3168, Australia. Electronic address: sebastian.hobson@monash.edu.
authors.forename: Sebastian R
authors.initials: SR
authors.lastname: Hobson
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia.
authors.forename: Rutu
authors.initials: R
authors.lastname: Acharya
authors.affiliation: Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia; The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia.
authors.forename: Siow Teng
authors.initials: ST
authors.lastname: Chan
authors.affiliation: Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia; Monash Women's Services, Monash Health, Clayton, VIC 3168, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Mockler
authors.affiliation: Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia; The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia; Monash Women's Services, Monash Health, Clayton, VIC 3168, Australia.
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
mesh_terms: D028341:Activins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D011247:Pregnancy; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D019010:Vascular Cell Adhesion Molecule-1; C422405:activin A; D028341:Activins; D018799:Intercellular Adhesion Molecule-1
keywords: Activin; Endothelin; Follistatin; ICAM; Preeclampsia; VCAM