title: Decidual natural killer cells regulate vessel stability: implications for impaired spiral artery remodelling.
abstract: Decidual NK (dNK) cells are present during uterine spiral artery remodelling, an event that is crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Spiral artery remodelling is impaired in the pregnancy complication pre-eclampsia. Although dNK cells are known to play active roles at the maternal-fetal interface, little is known about their effect on endothelial integrity, an important component of vessel stability. We present a study in which we have modelled dNK-endothelium interactions, using first-trimester dNK cells isolated from both normal pregnancies and those with impaired spiral artery remodelling. dNK cells were isolated from first-trimester pregnancies, screened by uterine artery Doppler ultrasound to determine resistance indices (RI) that relate to the extent of spiral artery remodelling. dNK culture supernatant from normal-RI pregnancies (but not high-RI pregnancies) destabilised endothelial tube-like structures in Matrigel, and normal-RI dNK cells induced endothelial intercellular adhesion molecule-1 and tumour necrosis factor-α expression to a greater extent than high-RI dNK cells. We have established a functional role for dNK cells in the disruption of endothelial structures and have suggested how impairment of this process may be contributing to the reduced vessel remodelling in pregnancies with a high uterine artery resistance index. These findings have implications for our understanding of the pathology of pre-eclampsia and other pregnancy disorders where remodelling is impaired.
authors.affiliation: Institute of Cardiovascular and Cell Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
authors.forename: Rupsha
authors.initials: R
authors.lastname: Fraser
authors.affiliation: Institute of Cardiovascular and Cell Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
authors.forename: Guy St J
authors.initials: GS
authors.lastname: Whitley
authors.affiliation: Fetal Medicine Unit, St. George's Hospital, Blackshaw Road, London SW17 0QT, United Kingdom.
authors.forename: Baskaran
authors.initials: B
authors.lastname: Thilaganathan
authors.affiliation: Institute of Cardiovascular and Cell Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom. Electronic address: jcartwri@sgul.ac.uk.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Cartwright
mesh_terms: D000328:Adult; D001158:Arteries / Q000000981:diagnostic imaging / Q000276:immunology; D002461:Cell Line, Transformed; D003656:Decidua / Q000098:blood supply / Q000000981:diagnostic imaging / Q000276:immunology*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000276:immunology*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000000981:diagnostic imaging / Q000276:immunology*; D010920:Placenta / Q000098:blood supply / Q000000981:diagnostic imaging / Q000276:immunology*; D011225:Pre-Eclampsia / Q000000981:diagnostic imaging / Q000276:immunology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000276:immunology*; D014463:Ultrasonography
keywords: Decidua; Endothelium; Natural killer; Pre-eclampsia; Remodelling; Spiral artery