title: Support for involvement of the renin-angiotensin system in dysplastic Barrett's esophagus.
abstract: OBJECTIVE
  Patients with dysplasia in Barrett's esophagus (BE) have a considerable risk of developing esophageal adenocarcinoma (EAC). The mucosal expression of the pro-inflammatory angiotensin II receptor type 1 (AT1R) is elevated in these patients, suggesting a role in carcinogenesis. The purpose of this study was to determine whether interference with the renin-angiotensin system (RAS) would influence downstream markers of carcinogenesis.
  
  
  METHODS
  Endoscopic mucosal biopsies from BE patients with low-grade dysplasia (LGD) were sampled before and after a three-week period of RAS-interfering treatment. Thirty patients were randomly allocated to enalapril (ACE inhibitor, 5 mg od), candesartan (AT1R antagonist, 8 mg od), or no drug. The expression of 12 proteins known to be associated with RAS and carcinogenesis was assessed using western blot.
  
  
  RESULTS
  We found altered expression of several proteins after enalapril treatment (decreased: NFκB, p = .043; NLRP3, p = .050; AMACR, p = .017; and caspase 3, p = .025; increased: p53, p = .050). Candesartan treatment was associated with increased iNOS expression (p = .033). No significant changes were seen in the no-drug group.
  
  
  CONCLUSIONS
  Interference with angiotensin II formation was associated with altered expression of inflammation- and carcinogenesis-related proteins. The present results speak in favor of involvement of angiotensin II in BE dysplasia, but the role of AT1R should be investigated further.
authors.affiliation: a Department of Gastrosurgical Research and Education , Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg , Sweden.
authors.forename: Svein Olav
authors.initials: SO
authors.lastname: Bratlie
authors.affiliation: a Department of Gastrosurgical Research and Education , Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg , Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Casselbrant
authors.affiliation: a Department of Gastrosurgical Research and Education , Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg , Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Edebo
authors.affiliation: a Department of Gastrosurgical Research and Education , Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg , Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Fändriks
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000473:pathology; D001562:Benzimidazoles / Q000008:administration & dosage*; D014408:Biomarkers, Tumor; D001713:Biphenyl Compounds; D004656:Enalapril / Q000008:administration & dosage*; D004724:Endoscopy; D064098:Esomeprazole / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011230:Precancerous Conditions / Q000473:pathology; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000008:administration & dosage; D012084:Renin-Angiotensin System; D012307:Risk Factors; D013548:Sweden; D062606:Tertiary Care Centers; D013777:Tetrazoles / Q000008:administration & dosage*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D014408:Biomarkers, Tumor; D001713:Biphenyl Compounds; D009363:Neoplasm Proteins; D054328:Proton Pump Inhibitors; D013777:Tetrazoles; D004656:Enalapril; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D064098:Esomeprazole; C081643:candesartan
keywords: Barrett’s esophagus; biomarker; cancer; endoscopy; renin–angiotensin system