PTH-138 TNF-A Dependent Angiopoeitin Mediated Angiogenesis in Sporadic Small Bowel Angiodysplasia; Novel Pathophysiology and Potential Clinical Marker

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Abstract

Introduction

Angiodysplasias account for over 50% of small bowel causes of obscure gastrointestinal bleeding. Angiodysplasias are thought to develop as a result of an imbalance in the angiogenic cascade, although the exact mechanism remains elusive. Previous research we have undertaken has associated elevated serum angiopoietin-2 (Ang-2) levels with angiodysplasia. Ang-1 and Ang-2 are ligands of the endothelial receptor tyrosine kinase Tie-2. Ang-1 regulates endothelial cell survival and blood vessel maturation and plays a key role in maintaining vascular integrity. Ang-2 is a functional antagonist of Ang-1. Inflammation and angiogenesis are associated with several pathological disorders and previous data suggests a TNF-α dependent dual functional roles of Tie2 in inflammatory angiogenesis

Methods

Following informed consent, serum samples were collected from patients with a definite diagnosis of sporadic small bowel angiodysplasia (P2) on capsule endoscopy, and from healthy controls in which GI bleeding had been out-ruled by a negative faecal immunochemical test. Serum levels of Ang-1, Ang-2 and TNF-α were measured using commercially available ELISA kits. All results were expressed as a mean and compared between patients and controls, and the mean of the ratio of ang2/ang1 levels for each group was calculated.

Results

A total of 80 samples were analysed for each factor, including 40 patients (48% male, average age 71 years) and 40 controls (43% male, average age 70 years). As expected and in keeping with our previous work levels of Ang-2 were significantly higher in patients (mean 4600 pg/ml) than in controls (mean 2973 pg/ml) p < 0.001. In addition levels of Ang-1 were significantly lower in the patient group (mean 13071 pg/ml) vs. controls (mean 21169 pg/ml) p < 0.004 (Table 1). We also found that levels of TNF-α were significantly lower in the patient group (mean 6.7 pg/ml) vs. controls (mean 12.2 pg/ml) p < 0.003. The mean of the ratio of Ang2/Ang1 levels was found to be significantly higher in patients (1.05) vs. controls (0.29) p < 0.05.

Conclusion

Ours is the first study to have identified a link between angiopoietin 1 and 2 ratios and gastrointestinal angiodysplasia. The TNF-α findings are also novel and would strongly suggest a role for inflammatory mediated angiogenesis in this condition.

Disclosure of Interest

None Declared.

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