Article Text

PDF

PTH-138 Tnf-a Dependent Angiopoeitin Mediated Angiogenesis In Sporadic Small Bowel Angiodysplasia; Novel Pathophysiology And Potential Clinical Marker
  1. G Holleran1,
  2. B Hall1,
  3. P Crotty2,
  4. S Smith3,
  5. D McNamara1
  1. 1Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland
  2. 2Department of Histopathology, Tallaght Hospital, Tallaght, Ireland
  3. 3Department of Clinical Medicine, Tallaght Hospital, Tallaght, Ireland

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.

Abstract PTH-138 Table 1

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.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.