title: Expression of Angiogenic Factors in Patients With Sporadic Small Bowel Angiodysplasia.
abstract: OBJECTIVE
  To identify putative angiogenic factors associated with sporadic small bowel angiodysplasia (SBA).
  
  
  BACKGROUND
  SBAs account for 50% of obscure gastrointestinal bleeding and due to delays in diagnosis and ineffective treatments, are associated with high levels of morbidity and mortality. Treatment development is impeded by a limited knowledge of the pathophysiology behind SBA formation.
  
  
  METHODS
  We identified patients with definite sporadic SBA, and fecal immunochemical-negative controls were recruited from our institution's colorectal cancer screening program. Serum levels of VEGF, endoglin, Angiopoietin-2 (Ang-2), PDGF, Angiopoietin-1 (Ang-1), and TNF-α were measured using commercially available enzyme-linked immunosorbent assay kits. On the basis of serum results, we measured gene expression of target angiogenic factors in small bowel biopsy samples from angiodysplasias and unaffected tissue by quantitative PCR assessment.
  
  
  RESULTS
  Serum samples were analyzed from 40 SBA patients and 40 controls. Median serum levels of Ang-2 were significantly higher in patients than controls with levels of Ang-1 and TNF-α significantly lower. There were no differences in serum levels of VEGF, endoglin, or PDGF. Gene expression levels of Ang-1, Ang-2, and their receptor Tie2 were all significantly higher in biopsies from areas of angiodysplasia compared with normal small bowel.
  
  
  CONCLUSIONS
  This study, the first to explore the role of angiogenic factors in SBA, has identified a positive association between SBA and the Angiopoietin pathway, with increased serum and mucosal expression of Ang-2, which could potentially be used as a serum biomarker and future therapeutic target to improve outcome in affected patients.
authors.affiliation: Departments of *Gastroenterology and Clinical Medicine, Tallaght Hospital †Biostatistics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Grainne
authors.initials: G
authors.lastname: Holleran
authors.forename: Barry
authors.initials: B
authors.lastname: Hall
authors.forename: Myra
authors.initials: M
authors.lastname: O'Regan
authors.forename: Sinead
authors.initials: S
authors.lastname: Smith
authors.forename: Deirdre
authors.initials: D
authors.lastname: McNamara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016888:Angiodysplasia / Q000097:blood* / Q000150:complications / Q000235:genetics; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D015703:Antigens, CD / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000235:genetics; D006801:Humans; D007410:Intestinal Diseases / Q000097:blood* / Q000150:complications / Q000235:genetics; D007421:Intestine, Small / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood; D012259:Ribonuclease, Pancreatic / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D033921:Vesicular Transport Proteins / Q000097:blood
chemical_list: D043925:Angiogenesis Inducing Agents; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; C555023:VPS51 protein, human; D042461:Vascular Endothelial Growth Factor A; D033921:Vesicular Transport Proteins; D042787:Receptor, TIE-2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic