Expression of angiotensin II receptor type 1 is reduced in advanced rat liver fibrosis.
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-beta, 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.
Töx
Ulrich
U
Department of Gastroenterology, University of Cologne, Cologne, Germany. ulrich.toex@uk-koeln.de
Scheller
Ingo
I
Kociok
Norbert
N
Kern
Michael André
MA
Klanac
Dejan
D
Daudi
Sharif Mohammed
SM
Laue
Oliver
O
Schirmacher
Peter
P
Goeser
Tobias
T
Schulte
Sigrid
S
Steffen
Hans Michael
HM
D000818:Animals; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D024042:Collagen Type I / Q000032:analysis; D018450:Disease Progression; D008099:Liver / Q000737:chemistry; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis*; D051899:Smad2 Protein / Q000032:analysis; D013777:Tetrazoles; D016212:Transforming Growth Factor beta / Q000032:analysis
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D024042:Collagen Type I; D044140:Receptor, Angiotensin, Type 1; D051899:Smad2 Protein; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D020778:Matrix Metalloproteinase 2; C077793:candesartan cilexetil