P096. Circulating components of the alternative renin–angiotensin system are upregulated in patients with inflammatory bowel disease
M. Garg1, L. Burrell2, E. Velkoska2, K. Griggs2, P. Angus3, P. Gibson4, J. Lubel1, 1Monash University, Gastroenterology, Eastern Health, Box Hill, Australia, 2University of Melbourne, Departments of Medicine and Cardiology, Heidelberg, Australia, 3University of Melbourne, Austin Hospital Liver Transplant Unit, Heidelberg, Australia, 4Monash University, Gastroenterology, The Alfred Hospital, Prahran, Australia
There is accumulating evidence that the renin–angiotensin system (RAS) is active within the gastrointestinal tract, but its influence in intestinal inflammation, especially inflammatory bowel disease (IBD), is poorly understood.
Aim: To measure the circulating concentration of RAS enzymes and peptide products in patients with IBD and healthy controls, and to correlate these with markers of disease activity.
Healthy controls, and patients with Crohn's disease (CD) and ulcerative colitis (UC) were studied. Demographic and clinical data together with plasma concentrations of the classical RAS components – angiotensin converting enzyme (ACE) and angiotensin II (Ang II) – and alternative RAS – ACE2 and Ang (1–7) – were analysed by radioimmuno- and enzymatic assays. Systemic inflammation was assessed using serum C-reactive protein, white cell count, platelet count, and albumin, and intestinal inflammation by faecal calprotectin. Participants taking ACE inhibitors and angiotensin receptor blockers were excluded.
19 healthy controls (11 female; mean age 38, range 23–68 y), 19 patients with CD (11 female; aged 45, range 23–76 y) and 15 with UC (6 female; aged 42, 26–64 y) were studied. The 3 groups were demographically similar. The classical RAS components were not significantly different across the three groups, whereas ACE2 activity and Ang (1–7) concentrations were higher in patients with IBD compared to controls, (ACE2; 21.5 vs 13.3 pmol/ml/min; p < 0.05, Ang (1–7); 22.8 vs 14.1 pg/ml; p < 0.001). Ang (1–7) demonstrated a weak correlation with platelet count and white cell count, but not calprotectin or C-reactive protein in patients with IBD.
|No.||Classical RAS||Alternative RAS|
|ACE (U/L)||Ang II (pg/ml)||ACE2 (pmol/ml/min)||Ang(1–7) (pg/ml)|
|Healthy controls||19||22.1 (17.1–27.2)||17.2 (10.6–23.9)||13.3 (9.9–16.7)||14.1 (11.1–17.0)|
|IBD (all)||34||22.9 (19.3–26.5)||15.4 (10.9–19.8)||21.5 (17.2–25.9)**||22.8 (20.0–25.5)***|
|Crohn's disease||19||23.6 (18.3–28.9)||13.7 (10.8–16.7)||21.8 (16.5–27.2)*||25.0 (21.2–28.8)***|
|Ulcerative colitis||15||21.9 (16.8–27.1)||17.4 (7.4–27.5)||21.1 (13.1–29.2) **||19.9 (16.2–23.7)***|
|Values are mean (95% CI).|
*P < 0.01 v. control (t-test), **P < 0.005, ***P < 0.001.
The alternative RAS axis is upregulated in patients with IBD, and Ang (1–7) correlates with some markers of disease activity. Further research into this novel pathway in IBD is indicated.