The discovery that renin–angiotensin system (RAS) components are locally expressed in the liver tissue, pointed out to a role for this system in the pathogenesis of hepatic fibrosis and cirrhosis. The RAS counter-regulatory axis composed by the angiotensin converting enzyme 2 (ACE2), angiotensin-(1-7) [Ang-(1-7)] and Mas receptor mediates pro-inflammatory, pro-thrombotic, and pro-fibrotic processes, frequently opposing the classical RAS arm (ACE-Ang II-AT1 receptor) actions. Therefore, the balance between both RAS axes most likely affects the clinical and histopathological expression of liver diseases. It is worth noticing that liver diseases are major causes of morbidity and mortality worldwide. Without proper treatment, all types of chronic hepatitis will progress to end-stage liver diseases, including cirrhosis, liver failure, and hepatocellular carcinoma, which ultimately lead to death. In this context, to better comprehend the role of RAS components in liver failure might pave the way for the search of potential predictive biomarkers as well as the development of novel therapeutic approaches. Valuable data have been generated from preclinical and clinical studies. Herein, we summarize the current evidence, mainly focusing in the ACE2-Ang-(1-7)-Mas receptor arm, regarding the role of RAS in liver diseases. The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.
KeywordsRenin–angiotensin system Angiotensin converting enzyme (ACE) Angiotensin II Angiotensin-(1-7) Mas receptors Hepatic cirrhosis Liver fibrosis
The authors would like to thank FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for financial support. ACSS is a CNPq productivity fellowship recipient. ASM is a 2016 NARSAD Young Investigator Grant Awardee from the Brain and Behavior Research Foundation.
Conflict of interest
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