Cited by 114Pregnancy and preeclampsia studiesReproductive System and PregnancyCell death mechanisms and regulation

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Fetal-Derived Trophoblast Use the Apoptotic Cytokine Tumor Necrosis Factor-α–Related Apoptosis-Inducing Ligand to Induce Smooth Muscle Cell Death

Keogh, Rosemary J., Harris, Lynda K., Freeman, Abigail, Baker, Philip N., Aplin, John D., Whitley, Guy StJ., Cartwright, Judith E.·2007·Circulation Research

DOI 10.1161/01.res.0000261352.81736.37

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Abstract

Remodeling of the uterine spiral arteries during pregnancy transforms them from high to low resistance vessels that lack vasoconstrictive properties. This process is essential to meet the demand for increased blood flow imposed by the growing fetus. Loss of endothelial and smooth muscle cells (SMC) is evident in remodeled arteries but the mechanisms underlying this transformation remain unknown. This study investigated the hypothesis that fetal trophoblast invading from the placenta instigate remodeling by triggering cell death in vascular SMC. Specifically, a role for trophoblast-derived death inducing cytokine tumor necrosis factor-α–related apoptosis-inducing ligand (TRAIL) was investigated. Expression of the activating TRAIL receptors R1 and R2 was detected by flow cytometry on human aortic SMC and by immunohistochemistry on spiral artery SMC. Recombinant human TRAIL induced human aortic SMC apoptosis, which was inhibited by antibodies against TRAIL-R1 or -R2. Perfusion of denuded spiral artery segments with recombinant human TRAIL also induced SMC apoptosis. Trophoblasts isolated from first trimester placenta expressed membrane-associated TRAIL and induced apoptosis of human aortic SMC; apoptosis was significantly inhibited by a recombinant human TRAIL-R1:Fc construct. Trophoblast within the first trimester placental bed also expressed TRAIL. These data show that: 1) TRAIL causes SMC death; 2) trophoblast produce the apoptotic cytokine TRAIL; and 3) trophoblast induce SMC apoptosis via a TRAIL-dependent mechanism. We conclude that TRAIL produced by trophoblast causes apoptosis of SMC and thus may contribute to SMC loss during spiral artery remodeling in pregnancy.

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Authors: Keogh, R. J., Harris, L. K., Freeman, A., Baker, P. N., Aplin, J. D., Whitley, G. S., & Cartwright, J. E.
Affiliations: St George's, University of London (GB)
From the Centre for Developmental and Endocrine Signalling, Division of Basic Medical Sciences (R.J.K., A.F., G.StJ.W., J.E.C.), St. George’s, University of London, Cranmer Terrace, London, UK; and Division of Human Development (L.K.H., P.N.B., J.D.A.), University of Manchester, St. Mary’s Hospital, Hathersage Road, Manchester, UK.
ORCID: Harris, Lynda K.
Baker, Philip N.
Aplin, John D.
Cartwright, Judith E.
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2007-03-30
Volume: 100
Issue: 6
Pages: 834-841
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/01.res.0000261352.81736.37
OpenAlex: W2151162913
Cited by: 114
References: 36
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 7 · 2014: 1 · 2013: 6 · 2012: 6
FWCI: 15.97
Type: journal article
Language: en
Open access: closed
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
St George's Online Research Archive (St George's University of London) (acceptedVersion)
Funders: Wellcome Trust (069939)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: tumor necrosis factor-related apoptosis-inducing ligand, TRAIL, trophoblast, smooth muscle cell apoptosis, spiral artery remodeling, uterine spiral arteries, TRAIL receptors, placenta, pregnancy, vascular remodeling, apoptosis
MeSH terms: Arteries, Cells, Cultured, Decidua, Female, Fetus, Humans, Muscle, Smooth, Vascular, Myometrium, Pregnancy, Pregnancy Trimester, First, Time Factors, Trophoblasts, Apoptosis, Receptors, Tumor Necrosis Factor, Microscopy, Video, Receptors, TNF-Related Apoptosis-Inducing Ligand, TNF-Related Apoptosis-Inducing Ligand

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Fetal-Derived Trophoblast Use the Apoptotic Cytokine Tumor Necrosis Factor-α–Related Apoptosis-Inducing Ligand to Induce Smooth Muscle Cell Death

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