In:
Hepatology Research, Wiley, Vol. 43, No. 11 ( 2013-11), p. 1241-1250
Kurzfassung:
Renin is a rate‐limiting enzyme of the renin–angiotensin system ( RAS ), and several reports have shown that renin plays an important role in several pathological processes. Although RAS is known to play a pivotal role in the progression of non‐alcoholic steatohepatitis ( NASH ), the role of renin is still obscure. The aim of the current study was to examine the effect of the clinically used direct renin inhibitor ( DRI ), aliskiren, on the progression of NASH in a rat model. Methods The effects of DRI on the choline‐deficient L ‐amino acid‐defined ( CDAA ) diet‐induced rat NASH model was examined in conjunction with the activated hepatic stellate cells ( A c‐ HSC ) and neovascularization, both of which are known to play important roles in liver fibrosis development and hepatocarcinogenesis, respectively. Results DRI exerted a marked inhibitory effect against liver fibrosis development and glutathione‐ S ‐transferase placental form ( GST ‐ P ) positive preneoplastic lesions along with suppression of the A c‐ HSC and neovascularization in a dose‐dependent manner. DRI also inhibited the hepatic expressions of transforming growth factor‐beta 1 ( TGF ‐beta 1), angiotensin‐ II ( AT‐II ) and vascular endothelial growth factor ( VEGF ). These results indicated that renin played a pivotal role in the liver fibrosis development and hepatocarcinogenesis of NASH . Conclusion Because DRI is already widely used in the clinical practice with safety, this drug may represent a potential new strategy against the progression of NASH in the future.
Materialart:
Online-Ressource
ISSN:
1386-6346
,
1872-034X
DOI:
10.1111/hepr.2013.43.issue-11
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2013
ZDB Id:
2006439-1