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Title: Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) levels in experimental biliary fibrosis.
Austin 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: Medicine (University of Melbourne)
Issue Date: 2-Apr-2007
Publication information: 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.
DOI: 10.1016/j.jhep.2007.03.008
Journal: Journal of Hepatology
Type: Journal Article
Subjects: Angiotensin I.genetics.metabolism.pharmacology
Bile Ducts
Gene Expression
In Vitro Techniques
Liver.blood supply.metabolism
Liver Cirrhosis, Biliary.metabolism
Liver Cirrhosis, Experimental
Peptide Fragments.genetics.metabolism.pharmacology
Peptidyl-Dipeptidase A.blood.genetics.metabolism
Portal Vein.drug effects
Proto-Oncogene Proteins.metabolism
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1.metabolism
Receptors, G-Protein-Coupled.metabolism
Appears in Collections:Journal articles

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