Review
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2017; 23(19): 3396-3406
Published online May 21, 2017. doi: 10.3748/wjg.v23.i19.3396
Renin angiotensin system in liver diseases: Friend or foe?
Ana Cristina Simões e Silva, Aline S Miranda, Natália P Rocha, Antônio L Teixeira
Ana Cristina Simões e Silva, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil
Ana Cristina Simões e Silva, Aline S Miranda, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, UFMG, Belo Horizonte, MG 30130-100, Brazil
Aline S Miranda, Laboratory of Neurobiology, Department of Morphology, Institute of Biological Sciences, UFMG, Belo Horizonte, MG 30130-100, Brazil
Natália P Rocha, Antônio L Teixeira, Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, United States
Author contributions: Simões e Silva AC and Teixeira AL designed the article; Miranda AS and Rocha NP performed literature search; Simões e Silva AC, Miranda AS, Rocha NP and Teixeira AL wrote and reviewed the paper.
Supported by CNPq, No. 460334/2014-0; and FAPEMIG, No. CDS - PPM-00555-15.
Conflict-of-interest statement: Simões e Silva AC, Miranda AS, Rocha NP and Teixeira AL declare no conflict of interest related to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ana Cristina Simões e Silva, MD, PhD, Professor, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, UFMG, Alfredo Balena Avenue, Number 190, 2nd floor, Room 281, Belo Horizonte, MG 30130-100, Brazil. acssilva@hotmail.com
Telephone: +55-31-34098073 Fax: +55-31-34099770
Received: January 28, 2017
Peer-review started: February 8, 2017
First decision: March 3, 2017
Revised: March 17, 2017
Accepted: April 12, 2017
Article in press: April 12, 2017
Published online: May 21, 2017
Abstract

In the last three decades, the understanding of the renin angiotensin system (RAS) has been changed by the discoveries of functional local systems, novel biologically active peptides, additional specific receptors, alternative pathways of angiotensin (Ang) II generation, and new roles for enzymes and precursor components other than those in Ang II synthesis. In this regard, the discovery that Ang-(1-7) opposes the pressor, proliferative, pro-fibrotic, and pro-inflammatory effects mediated by Ang II has contributed to the realization that the RAS is composed of two axes. The first axis consists of the angiotensin-converting enzyme (ACE), with Ang II as the end product, and the angiotensin type 1 (AT1) receptor as the main effector mediating the biological actions of Ang II. The second axis results from ACE2-mediated hydrolysis of Ang II, leading to the production of Ang-(1-7), with the Mas receptor as the main effector conveying the vasodilatory, anti-proliferative, anti-fibrotic, and anti-inflammatory effects of Ang-(1-7). Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver diseases. In this manuscript, we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications, including hemodynamic changes and hepatorenal syndrome. The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.

Keywords: Renin angiotensin system, Angiotensin II, Angiotensin-(1-7), Hepatic cirrhosis, Liver fibrosis, Hepatorenal syndrome

Core tip: This Editorial reports recent advances on the understanding of the renin angiotensin system in regard to the role of the two main and counter-regulatory mediators, Angiotensin II and Angiotensin-(1-7), in liver diseases and in their main complications. Experimental and clinical findings so far show that Angiotensin-(1-7) by binding to Mas receptor opposes Angiotensin II actions mediated by AT1 receptors in liver tissue, by eliciting anti-inflammatory, anti-oxidative and anti-fibrotic effects. This knowledge may help in paving the way for the development of novel treatments for liver diseases and their complications.