Evaluating the role of angiogenesis in disease behaviour and therapy response in ulcerative colitis
Citation:
Padraic McDonagh, 'Evaluating the role of angiogenesis in disease behaviour and therapy response in ulcerative colitis'. Trinity College Dublin. School of Medicine. Discipline of Clinical Microbiology. 2023Download Item:
Abstract:
Introduction
Ulcerative colitis (UC) is a chronic inflammatory condition with a significant impact on quality of life.
In this thesis two small molecule anti-angiogenic and anti-inflammatory agents were used to treat
tissue cultured media (TCM) from UC colonic explants. Targeting angiogenesis may provide a novel
therapeutic pathway in the management of UC.
Methods
Patients with a diagnosis of UC attending for a colonoscopy were offered the opportunity to
participate. The clinical characteristics of a UC patient cohort were evaluated. Two novel small
molecule drugs were used to treat active UC colonic explants. The colonic microenvironment was
investigated for angiogenic and inflammatory analyte expression. Both drugs were evaluated for
their ability to suppress the release of key inflammatory and angiogenic analytes.
Results
Both small molecule drugs led to a significant reduction in VEGF-A. VEGF-A is the most potent driver
of angiogenesis and has been shown to be associated with increased disease activity in IBD. Both
agents also had a significant anti-inflammatory effect, suppressing the secretion of TNF-α,
interleukin (IL)-2, IL-8, IL-12p70 and IL-13.
Conclusion
This study provides evidence that both small molecule agents may have a role in the management of
UC. Both molecules display strong anti-inflammatory and anti-angiogenic effects in the UC colonic
microenvironment.
Author: McDonagh, Padraic
Advisor:
Kevans, DavidO'Sullivan, Jacintha
Qualification name:
Doctor in Medicine (MD)Type of material:
ThesisCollections
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Full text availableKeywords:
Ulcerative colitis, angiogenesis, inflammatory bowel disease, dendritic cells, TNF-α, VEGFMetadata
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