Support for involvement of the renin–angiotensin system in dysplastic Barrett’s esophagus.

Background and aim: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. Conclusion: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. [ABSTRACT FROM PUBLISHER]