Celiac disease-specific TG2-targeted autoantibodies inhibit angiogenesis ex vivo and in vivo in mice by interfering with endothelial cell dynamics

Suvi Kalliokoski, Ana-Marija Sulic, Ilma R. Korponay-Szabó, Zsuzsa Szondy, Rafael Frias, Mileidys A. Perez, Stefania Martucciello, Anne Roivainen, Lauri J. Pelliniemi, Carla Esposito, Martin Griffin, Daniele Sblattero, Markku Mäki, Katri Kaukinen, Katri Lindfors, Sergio Caja

Research output: Contribution to journalArticle

Abstract

A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility.
LanguageEnglish
Article numbere65887
Number of pages8
JournalPLoS ONE
Volume8
Issue number6
DOIs
Publication statusPublished - 18 Jun 2013

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autoantibodies
celiac disease
protein-glutamine gamma-glutamyltransferase
Endothelial cells
Celiac Disease
angiogenesis
Autoantibodies
endothelial cells
Endothelial Cells
abdomen
Abdomen
mice
Assays
positron-emission tomography
Positron emission tomography
antibodies
Antibodies
assays
aorta
blood vessels

Bibliographical note

© 2013 Kalliokoski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite this

Kalliokoski, S., Sulic, A-M., Korponay-Szabó, I. R., Szondy, Z., Frias, R., Perez, M. A., ... Caja, S. (2013). Celiac disease-specific TG2-targeted autoantibodies inhibit angiogenesis ex vivo and in vivo in mice by interfering with endothelial cell dynamics. PLoS ONE, 8(6), [e65887]. https://doi.org/10.1371/journal.pone.0065887
Kalliokoski, Suvi ; Sulic, Ana-Marija ; Korponay-Szabó, Ilma R. ; Szondy, Zsuzsa ; Frias, Rafael ; Perez, Mileidys A. ; Martucciello, Stefania ; Roivainen, Anne ; Pelliniemi, Lauri J. ; Esposito, Carla ; Griffin, Martin ; Sblattero, Daniele ; Mäki, Markku ; Kaukinen, Katri ; Lindfors, Katri ; Caja, Sergio. / Celiac disease-specific TG2-targeted autoantibodies inhibit angiogenesis ex vivo and in vivo in mice by interfering with endothelial cell dynamics. In: PLoS ONE. 2013 ; Vol. 8, No. 6.
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abstract = "A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility.",
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Kalliokoski, S, Sulic, A-M, Korponay-Szabó, IR, Szondy, Z, Frias, R, Perez, MA, Martucciello, S, Roivainen, A, Pelliniemi, LJ, Esposito, C, Griffin, M, Sblattero, D, Mäki, M, Kaukinen, K, Lindfors, K & Caja, S 2013, 'Celiac disease-specific TG2-targeted autoantibodies inhibit angiogenesis ex vivo and in vivo in mice by interfering with endothelial cell dynamics' PLoS ONE, vol. 8, no. 6, e65887. https://doi.org/10.1371/journal.pone.0065887

Celiac disease-specific TG2-targeted autoantibodies inhibit angiogenesis ex vivo and in vivo in mice by interfering with endothelial cell dynamics. / Kalliokoski, Suvi; Sulic, Ana-Marija; Korponay-Szabó, Ilma R.; Szondy, Zsuzsa; Frias, Rafael; Perez, Mileidys A.; Martucciello, Stefania; Roivainen, Anne; Pelliniemi, Lauri J.; Esposito, Carla; Griffin, Martin; Sblattero, Daniele; Mäki, Markku; Kaukinen, Katri; Lindfors, Katri; Caja, Sergio.

In: PLoS ONE, Vol. 8, No. 6, e65887, 18.06.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Celiac disease-specific TG2-targeted autoantibodies inhibit angiogenesis ex vivo and in vivo in mice by interfering with endothelial cell dynamics

AU - Kalliokoski, Suvi

AU - Sulic, Ana-Marija

AU - Korponay-Szabó, Ilma R.

AU - Szondy, Zsuzsa

AU - Frias, Rafael

AU - Perez, Mileidys A.

AU - Martucciello, Stefania

AU - Roivainen, Anne

AU - Pelliniemi, Lauri J.

AU - Esposito, Carla

AU - Griffin, Martin

AU - Sblattero, Daniele

AU - Mäki, Markku

AU - Kaukinen, Katri

AU - Lindfors, Katri

AU - Caja, Sergio

N1 - © 2013 Kalliokoski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2013/6/18

Y1 - 2013/6/18

N2 - A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility.

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