Identification of novel circulating angiogenic factors in small bowel angiodysplasia: a further step towards delineating the pathophysiology and defining treatment targets

Abstract Background: Small bowel angiodysplasia (SBA) accounts for 50% of small bowel bleeding, with a poor prognosis due to inadequate response to limited treatments. A poor understanding of the pathophysiology of the condition impedes improvements in diagnosis and treatments. We previously identified the Angiopoietin pathway to be associated with SBA, however this may be only one of many angiogenic drivers. Methods: We initially measured relative levels of 55 angiogenic factors in serum of Small Bowel Angiodysplasia (SBA) patients and non-bleeding controls. Quantitative Enzyme-linked Immunosorbent Assay (ELISA) measurements of any significant factors detected were then performed in a larger group of patients and controls. Results: Serum measurements of relative levels of 55 angiogenic factors were performed in seven SBA patients and controls and identified significant differences in five factors between groups– Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2), Tissue-Inhibitor of Metalloproteinases 1 (TIMP1), Endostatin and Platelet-derived Growth Factor-AA (PDGF-AA). We found no differences in levels of Vascular Endothelial Growth Factor (VEGF). Quantitative serum ELISA measurements of TIMP1, Endostatin and PDGF-AA were performed in 20 SBA patients and controls and showed significantly lower mean levels of TIMP1 and higher levels of Endostatin in SBA patients compared to controls, with no differences in PDGF-AA levels. Conclusions: This study confirms our previous findings, that Ang1 and Ang2 are key factors associated with SBA formation, and that VEGF is unlikely to have a key role in SBA pathophysiology. We have identified two new anti-angiogenic factors likely to be involved in SBA development, TIMP1 and Endostatin. Further assessments of circulating and tissue levels of these factors may advance the discovery of the pathophysiology of SBA and identify therapeutic targets.