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- Title
Expression of Angiotensin II Receptor Type 1 Is Reduced in Advanced Rat Liver Fibrosis.
- Authors
Ingo Scheller; Norbert Kociok; Michael Kern; Dejan Klanac; Sharif Daudi; Oliver Laue; Peter Schirmacher; Tobias Goeser; Sigrid Schulte; Hans Steffen
- Abstract
Abstract  In this study, we assessed the hypothesis that the expression of angiotensin II receptor type 1 (AGTR1) in liver tissue changes with increasing fibrosis, which would influence the antifibrotic efficacy of AGTR1 blockers. Rats were treated with candesartancilexetil (CAN) initiated 8 or 15 days after bile duct occlusion (BDO). Four weeks after BDO, AGTR1 mRNA and protein were decreased compared to those in sham-operated animals depending on the amount of fibrosis. Starting CAN early, but not late, reduced mRNA of profibrotic TGF-β, MMP2, and Smad2. However, CAN had no significant effect on collagen I, fibrosis, or intrahepatic resistance. In conclusion, progression of liver fibrosis reduces AGTR1 expression. Therefore, in our model, antifibrotic effects of CAN are insufficient to improve fibrosis or intrahepatic resistance. However, if AGTR1 blockade is started early, a decrease in essential profibrotic molecules is achieved. Hence, early initiation of therapy with AGTR1 blockers may be crucial for the prevention of cirrhosis.
- Subjects
ANGIOTENSINS; NEUROPEPTIDES; OLIGOPEPTIDES; EXTRACELLULAR matrix proteins
- Publication
Digestive Diseases & Sciences, 2007, Vol 52, Issue 8, p1995
- ISSN
0163-2116
- Publication type
Article