Effect of angiotensin-converting enzyme inhibition on experimental hepatic fibrogenesis

Dig Dis Sci. 2008 Mar;53(3):789-93. doi: 10.1007/s10620-007-9941-y. Epub 2007 Sep 1.

Abstract

The renin-angiotensin system is suggested to be important in liver fibrogenesis. It induces hepatic stellate cell proliferation and up-regulates transforming growth factor beta-1 (TGF-beta1) expression. Matrix metalloproteinase-2 (MMP-2) is involved in extracellular matrix remodelling. Fibrosis, a consequence of most chronic liver diseases, may be the result of a disturbed balance between fibrogenesis and fibrolysis. The aim of this study was to investigate the effect of enalapril on liver fibrogenesis induced in rats by bile-duct ligation. Forty-seven rats were divided into two groups: bile-duct ligated (BDL) (n = 24) and BDL + enalapril (n = 23). Fibrosis was evaluated by the Knodell scoring system, and TGF-beta1 and MMP-2 were assessed with immunohistochemistry at the second, fourth and sixth weeks after bile-duct ligation. In the BDL group, TGF-beta1 increased by the second week and this increase continued through weeks 4 and 6. In the BDL + enalapril group, TGF-beta1 was significantly lower than the other group (P < 0.05). MMP-2 progressively decreased after week 2 in the BDL group. In the BDL + enalapril group, MMP-2 was significantly higher than the BDL group at the fourth and sixth weeks. These results suggest that enalapril reduces the liver tissue TGF-beta1 and has an ameliorating effect on the fibrosis markers TGF-beta1 and MMP-2.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Enalapril / therapeutic use*
  • Liver / pathology
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / prevention & control*
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Rats
  • Rats, Wistar
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Transforming Growth Factor beta1
  • Enalapril
  • Matrix Metalloproteinase 2