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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Kalliokoski, Suvi ; Sulic, Ana-Marija ; Korponay-Szabó, Ilma R. ; Szondy, Zsuzsa ; Frias, Rafael ; Perez, Mileidys Alea ; Martucciello, Stefania ; Roivainen, Anne ; Pelliniemi, Lauri J. ; Esposito, Carla ; Griffin, Martin ; Sblattero, Daniele ; Mäki, Markku ; Kaukinen, Katri ; Lindfors, Katri ; Caja, Sergio (2013)
  • Publisher: Public Library of Science
  • Journal: PLoS ONE, volume 8, issue 6 (issn: 1932-6203, eissn: 1932-6203)
  • Related identifiers: pmc: PMC3688809, doi: 10.1371/journal.pone.0065887
  • Subject: Elméleti orvostudományok | Animal Models | Endothelial Cells | Research Article | Molecular Cell Biology | Mathematics | Radiology | Vascular Biology | Mouse | fi=Biolääketieteet | en=Biomedicine| | Immune Response | Celiac Disease | Biophysics | Immunology | Biostatistics | Cellular Types | Orvostudományok | Biology | Gastroenterology and Hepatology | Nuclear medicine | Medicine | fi=Sisätaudit | en=Internal medicine| | Immunoglobulins | Cardiovascular | fi=Biokemia, solu- ja molekyylibiologia | en=Biochemistry, cell and molecular biology| | Cell Motility | PET imaging | Autoimmunity | Model Organisms | Extracellular Matrix | Statistics
    mesheuropmc: nutritional and metabolic diseases | digestive system diseases

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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