Imbalance of the renin-angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?
Adult
Angiotensin-Converting Enzyme Inhibitors
/ pharmacology
Benzimidazoles
/ pharmacology
Biphenyl Compounds
Cell Proliferation
/ drug effects
Cells, Cultured
Cohort Studies
Colon
/ cytology
Dose-Response Relationship, Drug
Drug Delivery Systems
Female
Fibrosis
/ drug therapy
Humans
Inflammatory Bowel Diseases
/ drug therapy
Male
Myofibroblasts
/ cytology
Renin-Angiotensin System
/ drug effects
Retrospective Studies
Sensitivity and Specificity
Tetrazoles
/ pharmacology
Renin-angiotensin system
angiotensin (1-7)
fibrosis
inflammatory bowel disease
myofibroblasts
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
14
02
2019
revised:
10
07
2019
accepted:
03
08
2019
pubmed:
15
8
2019
medline:
4
11
2020
entrez:
15
8
2019
Statut:
ppublish
Résumé
We evaluated the influence of the renin-angiotensin system (RAS) on intestinal inflammation and fibrosis. Cultured 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. Human 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. The 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.
Identifiants
pubmed: 31409604
pii: gutjnl-2019-318512
doi: 10.1136/gutjnl-2019-318512
doi:
Substances chimiques
Angiotensin-Converting Enzyme Inhibitors
0
Benzimidazoles
0
Biphenyl Compounds
0
Tetrazoles
0
candesartan
S8Q36MD2XX
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
841-851Commentaires et corrections
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.