title: Update on new aspects of the renin-angiotensin system in liver disease: clinical implications and new therapeutic options.
abstract: The RAS (renin-angiotensin system) is now recognized as an important regulator of liver fibrosis and portal pressure. Liver injury stimulates the hepatic expression of components of the RAS, such as ACE (angiotensin-converting enzyme) and the AT(1) receptor [AngII (angiotensin II) type 1 receptor], which play an active role in promoting inflammation and deposition of extracellular matrix. In addition, the more recently recognized structural homologue of ACE, ACE2, is also up-regulated. ACE2 catalyses the conversion of AngII into Ang-(1-7) [angiotensin-(1-7)], and there is accumulating evidence that this 'alternative axis' of the RAS has anti-fibrotic, vasodilatory and anti-proliferative effects, thus counterbalancing the effects of AngII in the liver. The RAS is also emerging as an important contributor to the pathophysiology of portal hypertension in cirrhosis. Although the intrahepatic circulation in cirrhosis is hypercontractile in response to AngII, resulting in increased hepatic resistance, the splanchnic vasculature is hyporesponsive, promoting the development of the hyperdynamic circulation that characterizes portal hypertension. Both liver fibrosis and portal hypertension represent important therapeutic challenges for the clinician, and there is accumulating evidence that RAS blockade may be beneficial in these circumstances. The present review outlines new aspects of the RAS and explores its role in the pathogenesis and treatment of liver fibrosis and portal hypertension.
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia. j.grace4@pgrad.unimelb.edu.au
authors.forename: Josephine A
authors.initials: JA
authors.lastname: Grace
authors.forename: Chandana B
authors.initials: CB
authors.lastname: Herath
authors.forename: Kai Yan
authors.initials: KY
authors.lastname: Mak
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
authors.forename: Peter W
authors.initials: PW
authors.lastname: Angus
mesh_terms: D000804:Angiotensin II / Q000235:genetics; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D006530:Hepatorenal Syndrome / Q000503:physiopathology; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013152:Splanchnic Circulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A