Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25994
Title: Update on New Aspects of the Renin-Angiotensin System in Hepatic Fibrosis and Portal Hypertension: Implications for Novel Therapeutic Options.
Austin Authors: Rajapaksha, Indu G;Gunarathne, Lakmie S;Angus, Peter W ;Herath, Chandana B
Affiliation: Gastroenterology and Hepatology
Medicine (University of Melbourne)
South Western Sydney Clinical School, Faculty of Medicine, Ingham Institute for Applied Medical Research, University of New South Wales, Liverpool, NSW 2170, Australia
Issue Date: 11-Feb-2021
metadata.dc.date: 2021-02-11
Publication information: Journal of Clinical Medicine 2021; 10(4): 702
Abstract: There is considerable experimental evidence that the renin angiotensin system (RAS) plays a central role in both hepatic fibrogenesis and portal hypertension. Angiotensin converting enzyme (ACE), a key enzyme of the classical RAS, converts angiotensin I (Ang I) to angiotensin II (Ang II), which acts via the Ang II type 1 receptor (AT1R) to stimulate hepatic fibrosis and increase intrahepatic vascular tone and portal pressure. Inhibitors of the classical RAS, drugs which are widely used in clinical practice in patients with hypertension, have been shown to inhibit liver fibrosis in animal models but their efficacy in human liver disease is yet to be tested in adequately powered clinical trials. Small trials in cirrhotic patients have demonstrated that these drugs may lower portal pressure but produce off-target complications such as systemic hypotension and renal failure. More recently, the alternate RAS, comprising its key enzyme, ACE2, the effector peptide angiotensin-(1-7) (Ang-(1-7)) which mediates its effects via the putative receptor Mas (MasR), has also been implicated in the pathogenesis of liver fibrosis and portal hypertension. This system is activated in both preclinical animal models and human chronic liver disease and it is now well established that the alternate RAS counter-regulates many of the deleterious effects of the ACE-dependent classical RAS. Work from our laboratory has demonstrated that liver-specific ACE2 overexpression reduces hepatic fibrosis and liver perfusion pressure without producing off-target effects. In addition, recent studies suggest that the blockers of the receptors of alternate RAS, such as the MasR and Mas related G protein-coupled receptor type-D (MrgD), increase splanchnic vascular resistance in cirrhotic animals, and thus drugs targeting the alternate RAS may be useful in the treatment of portal hypertension. This review outlines the role of the RAS in liver fibrosis and portal hypertension with a special emphasis on the possible new therapeutic approaches targeting the ACE2-driven alternate RAS.
URI: https://ahro.austin.org.au/austinjspui/handle/1/25994
DOI: 10.3390/jcm10040702
ORCID: 0000-0002-3326-3654
0000-0001-5841-057X
PubMed URL: 33670126
ISSN: 2077-0383
Type: Journal Article
Subjects: Mas related G protein-coupled receptor type-D
angiotensin converting enzyme 2
angiotensin-(1–7)
liver fibrosis and cirrhosis
portal hypertension
renin angiotensin system
Appears in Collections:Journal articles

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