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Expression of Angiotensin II Receptor Type 1 Is Reduced in Advanced Rat Liver Fibrosis

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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.

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Acknowledgments

This study was supported by a grant from the Marga and Walter Boll Stiftung. The authors thank Gudrun Suckau and Gitta Jakob for excellent technical assistance.

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Authors and Affiliations

  1. Department of Gastroenterology, University of Cologne, Cologne, Germany

    Ulrich Töx, Ingo Scheller, Dejan Klanac, Sharif Mohammed Daudi, Oliver Laue, Tobias Goeser, Sigrid Schulte & Hans Michael Steffen

  2. Department of Vitroretinal Surgery at the University Eye Hospital, University of Cologne, Cologne, Germany

    Norbert Kociok

  3. Institute of Pathology, University of Cologne, Cologne, Germany

    Michael André Kern & Peter Schirmacher

  4. Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Universität zu Köln, D-50924, Köln, Germany

    Ulrich Töx

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  1. Ulrich Töx
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Correspondence to Ulrich Töx.

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Töx, U., Scheller, I., Kociok, N. et al. Expression of Angiotensin II Receptor Type 1 Is Reduced in Advanced Rat Liver Fibrosis. Dig Dis Sci 52, 1995–2005 (2007). https://doi.org/10.1007/s10620-006-9133-1

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  • DOI: https://doi.org/10.1007/s10620-006-9133-1

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