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

doi: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

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 journal › Article › peer-review

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.

Original language	English
Article number	e65887
Number of pages	8
Journal	PLoS ONE
Volume	8
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0065887
Publication status	Published - 18 Jun 2013

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.

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10.1371/journal.pone.0065887

Celiac disease–specific TG2-targeted autoantibodies
© 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.
Final published version, 673 KBLicence: CC BY 3.0

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065887

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Kalliokoski, S., Sulic, A.-M., Korponay-Szabó, I. R., Szondy, Z., Frias, R., Perez, M. A., Martucciello, S., Roivainen, A., Pelliniemi, L. J., 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, 8(6), Article e65887. https://doi.org/10.1371/journal.pone.0065887

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

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.",

author = "Suvi Kalliokoski and Ana-Marija Sulic and Korponay-Szab{\'o}, {Ilma R.} and Zsuzsa Szondy and Rafael Frias and Perez, {Mileidys A.} and Stefania Martucciello and Anne Roivainen and Pelliniemi, {Lauri J.} and Carla Esposito and Martin Griffin and Daniele Sblattero and Markku M{\"a}ki and Katri Kaukinen and Katri Lindfors and Sergio Caja",

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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

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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.

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

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Erratum: Celiac disease-specific TG2-targeted autoantibodies inhibit angiogenesis ex vivo and in vivo in mice by interfering with endothelial cell dynamics (PLoS ONE (2014) 9:1)

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