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Trophoblast-induced changes in C-x-C motif chemokine 10 expression contribute to vascular smooth muscle cell dedifferentiation during spiral artery remodeling.

Wallace, AE; Cartwright, JE; Begum, R; Laing, K; Thilaganathan, B; Whitley, GS (2013) Trophoblast-induced changes in C-x-C motif chemokine 10 expression contribute to vascular smooth muscle cell dedifferentiation during spiral artery remodeling. Arteriosclerosis, Thrombosis, and Vascular Biology, 33 (3). e93 - e101 (9). ISSN 1079-5642 https://doi.org/10.1161/ATVBAHA.112.300354
SGUL Authors: Cartwright, Judith Eleanor Laing, Kenneth Wallace, Alison Elizabeth Whitley, Guy St John Thilaganathan, Baskaran

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Abstract

Objective- During pregnancy, fetal trophoblast disrupt endothelial cell and vascular smooth muscle cell (VSMC) interactions in spiral arteries of the maternal decidua to enable increased nutritional and oxygen delivery to the fetus. Little is known regarding this transformation because of difficulties of studying human pregnancy in vivo. This study investigated how trophoblast-secreted factors affect the interactions of vascular cells and the differentiation status of VSMC during spiral arteries remodeling using 3-dimensional vascular spheroid coculture. Methods and Results— Endothelial cell and VSMC were cocultured in hanging droplets to form spheroids representing an inverted vessel lumen. Control or conditioned media from an extravillous trophoblast (EVT) cell line was incubated with vascular spheroids for 24 hours. Spheroid RNA was then analyzed by Illumina Sentrix BeadChip array. Spheroids incubated with EVT conditioned medium showed significant up/downregulation of 101 genes (>1.5-fold; P<0.05), including an upregulation of C-X-C motif chemokine 10 (IP-10). C-X-C motif chemokine 10 expression was confirmed by qualitative real-time PCR and Western blot analysis of spheroids, and immunohistochemistry of first trimester decidua and ex vivo dissected nonplacental bed spiral arteries. EVT conditioned medium reduced VSMC expression of differentiation markers, and both EVT conditioned medium and C-X-C motif chemokine 10 increased motility of VSMC indicating dedifferentiation of VSMC. Conclusion— EVT-induced C-X-C motif chemokine 10 expression may contribute to spiral arteries remodeling during pregnancy by altering the motility and differentiation status of the VSMC in the vessel.

Item Type: Article
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: Arteriosclerosis, Thrombosis, and Vascular Biology
ISSN: 1079-5642
Dates:
DateEvent
1 March 2013Published
PubMed ID: 23288171
Web of Science ID: 23288171
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/100949
Publisher's version: https://doi.org/10.1161/ATVBAHA.112.300354

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