ObjectiveWe evaluated the influence of the renin–angiotensin system (RAS) on intestinal inflammation and fibrosis.DesignCultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1–7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies.ResultsHuman colonic myofibroblast proliferation was reduced by Ang (1–7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1–7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson’s trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=−0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation.ConclusionsThe RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.

Diagnostic-based patient selection and treatment is integral to optimal outcomes in CMV, and therefore we propose an algorithm based on these concepts that now requires prospective evaluation.

The burden of IBD in our local region is high. Demographic similarities allow these results to be applied to the broader Australian community. We propose that the number of existing and new cases each year in Australia has been previously underestimated. These revised figures will be important when planning the provision of health resources for these patients in the future and when assessing need for research funding priorities.