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

<p><b>Background and aim:</b> 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.</p> <p><b>Methods:</b> 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.</p> <p><b>Results:</b> We found altered expression of several proteins after enalapril treatment (decreased: NFκB, <i>p</i> = .043; NLRP3, <i>p</i> = .050; AMACR, <i>p</i> = .017; and caspase 3, <i>p</i> = .025; increased: p53, <i>p</i> = .050). Candesartan treatment was associated with increased iNOS expression (<i>p</i> = .033). No significant changes were seen in the no-drug group.</p> <p><b>Conclusion:</b> 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.</p