Proteomic Approach to the Potential Role of Angiotensin II in Barrett Dysplasia.

BACKGROUND AND AIM: Dysplasia in Barrett's esophagus (BE) is regarded as a pre-neoplastic lesion. The renin-angiotensin system (RAS), which is known for its role in electrolyte homeostasis and hemodynamics, has also been shown to have tissue-based features linked to proliferation, inflammation, and cancer. RAS has been found to be associated with BE dysplasia. The aim of this study was to investigate possible effects of the RAS in BE dysplasia by using RAS-interfering pharmaceutical agents and by assessment of global protein expression in esophageal mucosal biopsies.

METHODS: Endoscopic biopsies were taken from 18 BE in patients with low-grade dysplasia (LGD) before and after three weeks of treatment with either angiotensin-converting enzyme (ACE) inhibitors (enalapril 5 mg; n = 6) or angiotensin II receptor type 1 (AT1R) blockers (candesartan 8 mg; n = 6), or no-treatment (n = 6). A global proteomics analysis by 2-D gel electrophoresis and mass spectrometry (MS) was then performed to identify proteins that were regulated after interference with RAS. Criteria-based selection of the proteins of particular interest was performed in two steps.

RESULTS: Three proteins were identified to show significant modulation of expression after three weeks of treatment: 60 kDa heat shock protein (downregulated), protein disulphide isomerase A3 (downregulated), and inorganic pyrophosphatase (upregulated).

CONCLUSION: We detected three proteins with no previously known links to esophageal RAS, but with possible relevance for the development of EAC. The fact that expression of these proteins was influenced by interference with the RAS suggests an involvement of AngII in the development of EAC in BE. This article is protected by copyright. All rights reserved.