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 and Caja, Sergio (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),

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.

Publication DOI: https://doi.org/10.1371/journal.pone.0065887
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Aston University (General)
Additional Information: © 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.
Full Text Link: http://www.plos ... al.pone.0065887
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2013-06-18
Authors: 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

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