What do we know about the renin angiotensin system and inflammatory bowel disease?

ABSTRACT

Introduction

The renin-angiotensin system (RAS) is an important homeostatic pathway, with emerging evidence for the impact of its components on inflammation and fibrosis in gastrointestinal tissues. This review aims to review current knowledge of the physiological mechanism of RAS in inflammatory bowel disease (IBD), and potential therapeutic implications.

Areas covered

An extensive online literature review including Pubmed, Medline, and Google Scholar was undertaken. Discussion on the components of the RAS, localization, and physiological functions in the gastrointestinal tract, preclinical, and clinical data in IBD, and the relation with SARS-Cov-2 are covered in this review.

Expert Opinion

RAS inhibition may have a role as anti-fibrotic adjunct therapy. Targeting the local gastrointestinal RAS with novel modes of delivery may be a target for future therapeutics for IBD, given the widespread availability and safety of current options as utilized in other diseases. Further insight into the mechanism and downstream effects of gastrointestinal ACE2 may lead to a better understanding of the pathogenesis of IBD.

KEYWORDS:

• Angiotensin converting enzyme 2
• angiotensin converting enzyme inhibitor
• angiotensin receptor blocker
• gastrointestinal tract
• inflammatory bowel disease
• renin angiotensin system

Article highlights

• Components of the local RAS are present in the gastrointestinal tract, and exert numerous physiological effects

• RAS inhibition has anti-inflammatory and anti-fibrotic effects in murine colitis models

• An imbalance of the classical and alternative RAS components has been identified in patients with IBD

• Retrospective studies have shown effects of RAS inhibition in improving clinical outcomes

• SARS-Cov-2 and its relation to ACE2 has reignited interest in the RAS, aiding in elucidation of mechanism and downstream effects of gastrointestinal ACE2

• A possible role of RAS inhibition may be an adjunctive therapy in IBD, particularly for intestinal fibrosis

Declaration of interest

M. Garg has served on the advisory board of Pfizer and Pharmacosmos, and has received speaker fees, consultance fees, research or travel grants from: Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, and Pharmacosmos. J.P. Segal has received speaker fees from Takeda and Abbvie, and an unrestricted grant from Tillotts. J.S. Lubel has served on the advisory board for Gilead, Bayer, AbbVie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.