Liver fibrogenesis: a new role for the renin-angiotensin system.
Liver fibrosis is the consequence of chronic liver injury of any etiology. When advanced, fibrosis causes portal hypertension and liver insufficiency, and is a risk factor for developing hepatocellular carcinoma. In the last decade, there have been major advances in the knowledge of the pathogenesis of hepatic fibrosis. Hepatic stellate cells (HSCs) are recognized as the main collagen-producing cells in the injured liver, and key fibrogenic factors have been identified. Among these factors, the renin-angiotensin system (RAS) appears to play a major role. Angiotensin II (Ang II) mediates key biological actions involved in hepatic tissue repair, including myofibroblast proliferation, infiltration of inflammatory cells, and collagen synthesis. Activated HSCs secrete Ang II, which induces fibrogenic actions through the activation of NADPH oxidase. Importantly, the blockade of the RAS attenuates fibrosis development in different experimental models of chronic liver injury. Based on these studies, it has been proposed that the blockade of the RAS could be effective in preventing fibrosis progression in chronic liver diseases. Although no prospective studies have evaluated the antifibrotic effect of RAS inhibitors in patients with chronic liver diseases, controlled clinical trials are under way.
Bataller
Ramón
R
Institut de Malalties Digestives i Metabòliques, Hospital Clinic, IDIBAPS, Barcelona, Catalonia, Spain. bataller@clinic.ub.es
Sancho-Bru
Pau
P
Ginès
Pere
P
Brenner
David A
DA
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D005355:Fibrosis; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*; D012307:Risk Factors
D016207:Cytokines; D000804:Angiotensin II; D019255:NADPH Oxidases