The renin–angiotensin system in Barrett’s esophagus

Abstract

Objective: Barrett’s esophagus (BE) is a risk factor for esophageal adenocarcinoma. In addition to its classical endocrine character known for hemodynamic regulation, the renin–angiotensin system (RAS) can be associated with inflammation, wound healing, and cancer. The aim of this study was to explore a potential expression of the RAS in BE, with or without the presence of dysplasia.

Material and methods: Biopsy material was prepared for western blotting and immunohistochemistry. Non-BE patients (controls) were compared with BE patients regarding RAS in the squamous epithelium. In the columnar BE mucosa, RAS expression was studied in patients with and without dysplasia. Key components of the ‘classical’ RAS were assessed: the angiotensin-converting enzyme (ACE) and the angiotensin II subtype 1 and 2 receptors (AT1R and AT2R).

Results: The presence of RAS factors was confirmed in the esophageal mucosa of both control and BE patients. ACE protein expression was 48% lower (p = 0.001) whereas AT1R was 45% higher (p = 0.039) in the squamous epithelium of BE patients compared to epithelia from non-BE controls. In the metaplastic intestinal-like epithelium, AT1R expression was 37% higher in BE patients with confirmed dysplasia than in patients without dysplasia (p = 0.009). Immunohistochemistry showed an altered distribution of RAS proteins in BE patients with dysplasia.

Conclusions: The differential RAS expression observed may prove to be useful as a biomarker or a pharmaceutical target.

Keywords:

• Barrett’s esophagus
• biomarkers
• endoscopy
• esophageal adenocarcinoma
• renin–angiotensin receptor

Acknowledgements

Technical assistance by Christina Ek, My Engström, Gunilla Bogren and Eva Een is gratefully acknowledged and we thank Sören Lundberg for reviewing the statistics.

Disclosure statement

The authors have no conflicts of interests.

Funding information

This study was supported by grants from the Swedish Research Council (VR medicine), the Gothenburg Medical Society, the ALF agreement of the Western Region (VGR), and the Capio Research Fund.