on October 21, 2004
Published online before print October 21, 2004, doi: 10.1161/01.ATV.0000148547.70187.89
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 15, 2004
Accepted on September 24, 2004
Uterine Spiral Artery Remodeling Involves Endothelial Apoptosis Induced by Extravillous Trophoblasts Through Fas/FasL Interactions
Sandra V. Ashton ;
From the Biochemistry and Immunology Department of Basic Medical Sciences (S.V.A., G.S.J.W., P.R.D., J.E.C.), St. George’s Hospital Medical School, Cranmer Terrace, London, UK; and Maternal and Fetal Research Centre (M.W., I.P.C., P.N.B.), St. Mary’s Hospital, Whitworth Park, Manchester, UK.
* To whom correspondence should be addressed. E-mail: j.cartwright{at}sghms.ac.uk.
Objective--Invasion of uterine spiral arteries by extravillous trophoblasts in the first trimester of pregnancy results in loss of endothelial and musculoelastic layers. This remodeling is crucial for an adequate blood supply to the fetus with a failure to remodel implicated in the etiology of the hypertensive disorder preeclampsia. The mechanism by which trophoblasts induce this key process is unknown. This study gives the first insights into the potential mechanisms involved.
Methods and Results--Spiral arteries were dissected from nonplacental bed biopsies obtained at Caesarean section, and a novel model was used to mimic in vivo events. Arteries were cultured with trophoblasts in the lumen, and apoptotic changes in the endothelial layer were detected after 20 hours, leading to loss of endothelium by 96 hours. In vitro, coculture experiments showed that trophoblasts stimulated apoptosis of primary decidual endothelial cells and an endothelial cell line. This was blocked by caspase inhibition and NOK2, a FasL blocking antibody. NOK2 also abrogated trophoblast-induced endothelial apoptosis in the vessel model.
Conclusions--Extravillous trophoblast induction of endothelial apoptosis is a possible mechanism by which the endothelium is removed, and vascular remodeling may occur in uterine spiral arteries. Fas/FasL interactions have an important role in trophoblast-induced endothelial apoptosis.
Key words: apoptosis • endothelium • trophoblast • pregnancy • arteries
This article has been cited by other articles:
 |
|
 |
|
  S. A. Bainbridge, J. M. Roberts, F. von Versen-Hoynck, J. Koch, L. Edmunds, and C. A. Hubel Uric acid attenuates trophoblast invasion and integration into endothelial cell monolayers Am J Physiol Cell Physiol, August 1, 2009; 297(2): C440 - C450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 J. McCormick, G. S. J. Whitley, P. Le Bouteiller, and J. E. Cartwright Soluble HLA-G regulates motility and invasion of the trophoblast-derived cell line SGHPL-4 Hum. Reprod., June 1, 2009; 24(6): 1339 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Torricelli, L. Galleri, C. Voltolini, G. Biliotti, P. Florio, M. De Bonis, and F. Petraglia Changes of Placental Kiss-1 mRNA Expression and Maternal/Cord Kisspeptin Levels at Preterm Delivery Reproductive Sciences, October 1, 2008; 15(8): 779 - 784. [Abstract] [PDF]
|
|
|
|
|
|
H. L. LaMarca, P. R. Dash, K. Vishnuthevan, E. Harvey, D. E. Sullivan, C. A. Morris, and G. St. J. Whitley Epidermal growth factor-stimulated extravillous cytotrophoblast motility is mediated by the activation of PI3-K, Akt and both p38 and p42/44 mitogen-activated protein kinases Hum. Reprod., August 1, 2008; 23(8): 1733 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Detmar, M. Y. Rennie, K. J. Whiteley, D. Qu, Y. Taniuchi, X. Shang, R. F. Casper, S. L. Adamson, J. G. Sled, and A. Jurisicova Fetal growth restriction triggered by polycyclic aromatic hydrocarbons is associated with altered placental vasculature and AhR-dependent changes in cell death Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E519 - E530. [Abstract] [Full Text] [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]
|
|
|
|
|
|
R. J. Keogh, L. K. Harris, A. Freeman, P. N. Baker, J. D. Aplin, G. StJ. Whitley, and J. E. Cartwright Fetal-Derived Trophoblast Use the Apoptotic Cytokine Tumor Necrosis Factor-{alpha}-Related Apoptosis-Inducing Ligand to Induce Smooth Muscle Cell Death Circ. Res., March 30, 2007; 100(6): 834 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Harris, R. J. Keogh, M. Wareing, P. N. Baker, J. E. Cartwright, J. D. Aplin, and G. S. J. Whitley Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism Am. J. Pathol., November 1, 2006; 169(5): 1863 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fons, S. Chabot, J. E. Cartwright, F. Lenfant, F. L'Faqihi, J. Giustiniani, J.-P. Herault, G. Gueguen, F. Bono, P. Savi, et al. Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells Blood, October 15, 2006; 108(8): 2608 - 2615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Gultice, K. L. Selesniemi, and T. L. Brown Hypoxia Inhibits Differentiation of Lineage-Specific Rcho-1 Trophoblast Giant Cells Biol Reprod, June 1, 2006; 74(6): 1041 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Straszewski-Chavez, V. M. Abrahams, and G. Mor The Role of Apoptosis in the Regulation of Trophoblast Survival and Differentiation during Pregnancy Endocr. Rev., December 1, 2005; 26(7): 877 - 897. [Abstract] [Full Text] [PDF]
|
|