title: The role of renin-angiotensin system modulation on treatment and  prevention of liver diseases.
abstract: The renin-angiotensin system (RAS) is now recognized as an important modulator of body metabolic processes. The discovery of angiotensin-converting enzyme 2 (ACE2) has renewed interest in the potential therapeutic role of RAS modulation. Recent studies have pointed out the importance of the local balance between ACE/Ang-II/AT1 and ACE2/Ang-(1-7)/Mas arms to avoid liver metabolic diseases. Furthermore, non-alcoholic fatty liver disease is an increasing health problem that includes a spectrum of hepatic steatosis, steatohepatitis and fibrosis. Some new studies revealed that RAS imbalance appears to promote hepatic fibrogenesis; while the activation of ACE2/Ang-(1-7)/Mas counter-regulatory axis is able to prevent liver injuries. In this context, the aim of the present review is to discuss the importance of RAS in the development and prevention of liver disease. AT1 receptor activation by Ang II induces hepatic stellate cell contraction and proliferation, causes oxidative stress, endothelial dysfunction, cell growth and inflammation. In addition, both AT1 blocker administration and ACE inhibitors lead to a reduction in inflammation and improvement of hepatic fibrosis. Conversely, Ang-(1-7) infusion reduces fibrosis and proliferation mainly by suppression of hepatic stellate cell activation; Mas receptor antagonism aggravates liver fibrosis and severe liver steatosis. In conclusion, the use of ACE/Ang II/AT1 axis inhibitors associated with ACE2/Ang(1-7)/Mas axis activation is a promising new strategy serving as a novel therapeutic regimen to prevent and treat chronic liver diseases as well as acute liver injury.
authors.forename: Simone
authors.initials: S
authors.lastname: Moreira de Macêdo
authors.forename: Talita Antunes
authors.initials: TA
authors.lastname: Guimarães
authors.forename: John David
authors.initials: JD
authors.lastname: Feltenberger
authors.forename: Sérgio Henrique
authors.initials: SH
authors.lastname: Sousa Santos
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)