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J Hepatol. 2005 Aug;43(2):317-23.

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

Author information

1
Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.

Abstract

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.

PMID:
15964094
DOI:
10.1016/j.jhep.2005.02.034
[Indexed for MEDLINE]

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