Digestive Diseases and Sciences

, Volume 58, Issue 5, pp 1271–1281 | Cite as

Telmisartan Plus Propranolol Improves Liver Fibrosis and Bile Duct Proliferation in the PSC-Like Abcb4−/− Mouse Model

  • Susanne Mende
  • Sigrid Schulte
  • Ingo Strack
  • Heike Hunt
  • Margarete Odenthal
  • Galyna Pryymachuck
  • Maria Quasdorff
  • Münevver Demir
  • Dirk Nierhoff
  • Hans-Peter Dienes
  • Tobias Goeser
  • Hans-Michael Steffen
  • Ulrich Töx
Original Article



Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to cirrhosis and cholangiocellular carcinoma. Inhibitors of the renin–angiotensin system or the sympathetic nervous system delay liver fibrogenesis in animal models.


We investigated the antifibrotic potential of telmisartan, an angiotensin II type 1 receptor antagonist, and the β-adrenoceptor blocker propranolol in the PSC-like Abcb4 knockout mouse model.


Sixty-five Abcb4−/− mice were treated with telmisartan for 3 or 5 months (T) and with telmisartan plus propranolol for 3, 5, or 8 months (TP), or for 2 or 5 months starting with a delay of 3 months (TP delayed). Liver hydroxyproline content, inflammation, fibrosis, and bile duct proliferation were assessed; fibrosis-related molecules were analyzed by real-time polymerase chain reaction and Western blotting.


Compared to controls, telmisartan monotherapy had no significant influence on hydroxyproline; however, telmisartan plus propranolol reduced hydroxyproline (TP 3 months, p = 0.008), fibrosis score (TP 3 months and TP 8 months, p = 0.043 and p = 0.008, respectively; TP delayed 8 months, p < 0.0005), bile duct proliferation (TP 8 months and TP delayed 8 months, p = 0.006 and p < 0.0005, respectively), and procollagen α1(I), endothelin-1, TIMP-1 and MMP3 mRNA as well as α-SMA, CK-19, and TIMP-1 protein.


Telmisartan plus propranolol reduces liver fibrosis and bile duct proliferation in the PSC-like Abcb4−/− mouse model, even when started at late stages of fibrosis, and may thus represent a novel therapeutic option for cholestatic liver diseases such as PSC.


Abcb4 knockout AT1R-blocker Beta blocker Sclerosing cholangitis Fibrogenesis 



α-Smooth muscle actin



Ang II

Angiotensin II


Angiotensin converting enzyme


Angiotensin II type 1 receptor


Angiotensin II type 1 receptor blocker


Connective tissue growth factor






Extracellular matrix


Hepatic stellate cell


Matrix metalloproteinase


Primary sclerosing cholangitis


Procollagen α1(I)


Real-time quantitative reverse transcription polymerase chain reaction


Renin–angiotensin system


Sympathetic nervous system


Tissue inhibitor of matrix metalloproteinase

Supplementary material

10620_2012_2499_MOESM1_ESM.doc (150 kb)
Supplementary material 1 (DOC 149 kb)


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Susanne Mende
    • 1
  • Sigrid Schulte
    • 1
  • Ingo Strack
    • 2
  • Heike Hunt
    • 2
    • 3
  • Margarete Odenthal
    • 2
  • Galyna Pryymachuck
    • 1
  • Maria Quasdorff
    • 1
  • Münevver Demir
    • 1
  • Dirk Nierhoff
    • 1
  • Hans-Peter Dienes
    • 2
  • Tobias Goeser
    • 1
  • Hans-Michael Steffen
    • 1
  • Ulrich Töx
    • 1
  1. 1.Department of Gastroenterology and HepatologyUniversity Hospital of CologneCologneGermany
  2. 2.Institute for PathologyUniversity Hospital of CologneCologneGermany
  3. 3.Department of PathologyUniversity of North Carolina at Chapel HillChapel HillUSA

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