Platelet activation by activated von Willebrand factor is a marker of intestinal wound healing in patients with Crohn's disease

T. Manon-Jensen, L. Langholm, S. Sun, J. H. Mortensen, Y. He, A. Krag, M. D. Jensen, A. -C. Bay-Jensen, J. Kjeldsen, M. A. Karsdal

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Abstract

Background Crohn’s disease (CD) is a chronic inflammatory condition of the intestinal tract resulting in ongoing tissue damage and impaired wound healing. The reduced ability of CD patients to heal damaged tissue is reflected by the tendency of CD patients to develop fistula and fibrosis. ADATMS13-activation of von Willebrand factor (VWF) generate activated VWF and is essential in initiation of the primary response of wound healing, as activated VWF is a rate limiting factor in binding and activation of platelets to the damaged endothelium. Any dysregulation of VWF processing could contribute to the development and progression of CD, consequent to impaired and dysregulated wound healing, leading to a failure in the secondary wound healing response. We investigated the processing of VWF, a marker of endothelial dysfunction, in patients with CD. Methods We developed two biomarkers specifically targeting the ADAMTS13-processed form of VWF (VWF-A), and formation of VWF by quantification of the pro-peptide (VWF-N). Serum samples from 13 irritable bowel syndrome (IBS) patients with high-grade inflammation and 51 CD patients and were included in the study together with 10 age-matched healthy subjects. Results Levels of VWF-N (p < 0.05; p < 0.0001) and VWF-A (p < 0.05; p < 0.01) and were significantly increased in CD and IBS patients compared with healthy subjects (Figure1). VWF-N level (p < 0.001) discriminated CD and IBS patients from healthy subjects with a diagnostic accuracy of 94 %. No significant differences were observed in the ratio of VWF-N/VWF-A between CD, IBS and healthy subjects. Conclusions CD and IBS patients had both increased formation, but most importantly increased activated VWF, indicating a sustained elevated primary wound healing response as compared with healthy subjects. Biomarkers of wound healing could serve as supplementary markers of intestinal healing in patients with inflammatory bowel diseases.
Original languageEnglish
Article numberP265
JournalJournal of Crohn's and Colitis
Volume12
Issue numberSuppl. 1
Pages (from-to)S234-S235
ISSN1873-9946
DOIs
Publication statusPublished - 1. Feb 2018
Event13th Congress of the European Crohn’s and Colitis Organisation - Vienna, Austria
Duration: 14. Feb 201817. Feb 2018
Conference number: 13

Conference

Conference13th Congress of the European Crohn’s and Colitis Organisation
Number13
CountryAustria
CityVienna
Period14/02/201817/02/2018

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