Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10387
Title: Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) levels in experimental biliary fibrosis.
Authors: Herath, Chandana B;Warner, Fiona J;Lubel, John S;Dean, Rachael G;Jia, Zhiyuan;Lew, Rebecca A;Smith, A Ian;Burrell, Louise M;Angus, Peter W
Affiliation: Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Vic., Australia.
Issue Date: 2-Apr-2007
Citation: Journal of Hepatology 2007; 47(3): 387-95
Abstract: Angiotensin-converting enzyme 2 (ACE2), its product, angiotensin-(1-7) and its receptor, Mas, may moderate the adverse effects of angiotensin II in liver disease. We examined the expression of these novel components of the renin angiotensin system (RAS) and the production and vasoactive effects of angiotensin-(1-7) in the bile duct ligated (BDL) rat.BDL or sham-operated rats were sacrificed at 1, 2, 3 and 4 weeks. Tissue and blood were collected for gene expression, enzyme activity and peptide measurements. In situ perfused livers were used to assess angiotensin peptide production and their effects on portal resistance.Hepatic ACE2 gene and activity (P<0.0005), plasma angiotensin-(1-7) (P<0.0005) and Mas receptor expression (P<0.01) were increased following BDL compared to shams. Perfusion experiments confirmed that BDL livers produced increased angiotensin-(1-7) (P<0.05) from angiotensin II and this was augmented (P<0.01) by ACE inhibition. Whilst angiotensin II increased vasoconstriction in cirrhotic livers, angiotensin-(1-7) had no effect on portal resistance.RAS activation in chronic liver injury is associated with upregulation of ACE2, Mas and hepatic conversion of angiotensin II to angiotensin-(1-7) leading to increased circulating angiotensin-(1-7). These results support the presence of an ACE2-angiotensin-(1-7)-Mas axis in liver injury which may counteract the effects of angiotensin II.
Internal ID Number: 17532087
URI: http://ahro.austin.org.au/austinjspui/handle/1/10387
DOI: 10.1016/j.jhep.2007.03.008
URL: http://www.ncbi.nlm.nih.gov/pubmed/17532087
Type: Journal Article
Subjects: Angiotensin I.genetics.metabolism.pharmacology
Angiotensins.metabolism
Animals
Bile Ducts
Gene Expression
In Vitro Techniques
Ligation
Liver.blood supply.metabolism
Liver Cirrhosis, Biliary.metabolism
Liver Cirrhosis, Experimental
Male
Peptide Fragments.genetics.metabolism.pharmacology
Peptidyl-Dipeptidase A.blood.genetics.metabolism
Portal Vein.drug effects
Proto-Oncogene Proteins.metabolism
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1.metabolism
Receptors, G-Protein-Coupled.metabolism
Up-Regulation
Vasoconstriction
Appears in Collections:Journal articles

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