This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 100/6/834    most recent 01.RES.0000261352.81736.37v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Keogh, R. J. Articles by Cartwright, J. E. Search for Related Content PubMed PubMed Citation Articles by Keogh, R. J. Articles by Cartwright, J. E. Related Collections Remodeling Apoptosis Other Vascular biology Related Article

(Circulation Research. 2007;100:834.)
© 2007 American Heart Association, Inc.

Molecular Medicine

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

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

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.

Correspondence to Dr Judith E Cartwright, St George’s Hospital Medical School Department of Biochemistry and Immunology Cranmer Terrace London SW17 0RE United Kingdom. E-mail jcartwri{at}sgul.ac.uk

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-–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.

Key Words: apoptosis • cell death • pregnancy • vascular remodeling • vascular smooth muscle

Related Article:

Physiological Smooth Muscle Cell Apoptosis Contributes to the Uterine Vascular Remodeling in Human Early Pregnancy

Jean-Jacques Helwig and Philippe Le Bouteiller
Circ. Res. 2007 100: 754-756. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				P. C. Cavanagh, C. Dunk, M. Pampillo, J. M. Szereszewski, J. E. Taylor, C. Kahiri, V. Han, S. Lye, M. Bhattacharya, and A. V. Babwah Gonadotropin-releasing hormone-regulated chemokine expression in human placentation Am J Physiol Cell Physiol, July 1, 2009; 297(1): C17 - C27. [Abstract] [Full Text] [PDF]

				S. D. Smith, C. E. Dunk, J. D. Aplin, L. K. Harris, and R. L. Jones Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy Am. J. Pathol., May 1, 2009; 174(5): 1959 - 1971. [Abstract] [Full Text] [PDF]

				O M Faye-Petersen The placenta in preterm birth J. Clin. Pathol., December 1, 2008; 61(12): 1261 - 1275. [Abstract] [Full Text] [PDF]

				D. L. Langat, D. A. Wheaton, J. S. Platt, T. Sifers, and J. S. Hunt Signaling Pathways for B Cell-Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL) in Human Placenta Am. J. Pathol., May 1, 2008; 172(5): 1303 - 1311. [Abstract] [Full Text] [PDF]

				L. K. Harris and J. D. Aplin Vascular Remodeling and Extracellular Matrix Breakdown in the Uterine Spiral Arteries During Pregnancy Reproductive Sciences, December 1, 2007; 14(8_suppl): 28 - 34. [Abstract] [PDF]

				L.K. Harris, R.J. Keogh, M. Wareing, P.N. Baker, J.E. Cartwright, G.S. Whitley, and J.D. Aplin BeWo cells stimulate smooth muscle cell apoptosis and elastin breakdown in a model of spiral artery transformation Hum. Reprod., November 1, 2007; 22(11): 2834 - 2841. [Abstract] [Full Text] [PDF]

				J.-J. Helwig and P. Le Bouteiller Physiological Smooth Muscle Cell Apoptosis Contributes to the Uterine Vascular Remodeling in Human Early Pregnancy Circ. Res., March 30, 2007; 100(6): 754 - 756. [Full Text] [PDF]