Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) levels in experimental biliary fibrosis
BACKGROUND/AIMS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2007 |
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| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Journal of hepatology - 47(2007), 3 vom: 01. Sept., Seite 387-95 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Herath, Chandana B [VerfasserIn] |
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| Anmerkungen: |
Date Completed 03.12.2007 Date Revised 03.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM170542513 |
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| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Herath, Chandana B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) levels in experimental biliary fibrosis |
| 264 | 1 | |c 2007 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 03.12.2007 | ||
| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND/AIMS: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a RESULTS: 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 | ||
| 520 | |a CONCLUSIONS: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Angiotensins |2 NLM | |
| 650 | 7 | |a Peptide Fragments |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Mas |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
| 650 | 7 | |a Receptor, Angiotensin, Type 1 |2 NLM | |
| 650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
| 650 | 7 | |a Angiotensin I |2 NLM | |
| 650 | 7 | |a 9041-90-1 |2 NLM | |
| 650 | 7 | |a Peptidyl-Dipeptidase A |2 NLM | |
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| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a angiotensin I (1-7) |2 NLM | |
| 650 | 7 | |a IJ3FUK8MOF |2 NLM | |
| 700 | 1 | |a Warner, Fiona J |e verfasserin |4 aut | |
| 700 | 1 | |a Lubel, John S |e verfasserin |4 aut | |
| 700 | 1 | |a Dean, Rachael G |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Zhiyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Lew, Rebecca A |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, A Ian |e verfasserin |4 aut | |
| 700 | 1 | |a Burrell, Louise M |e verfasserin |4 aut | |
| 700 | 1 | |a Angus, Peter W |e verfasserin |4 aut | |
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