Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice.

Published

Journal Article

BACKGROUND/AIMS: Pharmacological blockade of the renin-angiotensin system (RAS) attenuates liver fibrogenesis in rats. Here, we provide genetic evidence implicating angiotensin type 1 (AT1) receptors in liver fibrogenesis. METHODS: Wild type (WT) and AT1a knockout [AT1a (-/-)] mice were subjected to either sham operation or bile-duct ligation. Fibrosis was assessed by Sirius Red staining and hydroxyproline hepatic content. Fibrogenic and inflammatory cytokines were measured by ELISA. RESULTS: Bile duct ligation-induced elevation of serum liver enzymes was similar in WT and AT1a (-/-) mice. Bile duct ligated WT mice showed inflammatory changes and severe septal fibrosis. In contrast, AT1a (-/-) mice showed minor fibrotic lesions. Collagen accumulation was lower in AT1a (-/-) mice compared to WT mice. The increase in hepatic concentration of TGFbeta1 and pro-inflammatory cytokines was attenuated in AT1a (-/-) mice compared to WT mice. Immunohistochemistry analysis revealed decreased infiltration by inflammatory cells, lipid peroxidation products as well as decreased phosphorylation of c-Jun and p42/44 MAPK in AT1a (-/-) mice compared to AT1 (+/+) mice. CONCLUSIONS: AT1 receptors play an important role in the development of fibrosis. Pharmacological blockade of AT1 receptors appears to be a promising approach to treat liver fibrosis.

Full Text

Duke Authors

Cited Authors

  • Yang, L; Bataller, R; Dulyx, J; Coffman, TM; Ginès, P; Rippe, RA; Brenner, DA

Published Date

  • August 2005

Published In

Volume / Issue

  • 43 / 2

Start / End Page

  • 317 - 323

PubMed ID

  • 15964094

Pubmed Central ID

  • 15964094

International Standard Serial Number (ISSN)

  • 0168-8278

Digital Object Identifier (DOI)

  • 10.1016/j.jhep.2005.02.034

Language

  • eng

Conference Location

  • Netherlands