title: The role of the renin-angiotensin system in liver fibrosis.
abstract: Hepatic fibrosis, which is characterized by progressive inflammation and deposition of extracellular matrix components, is a common response to chronic liver disease. Hepatic fibrogenesis is a dynamic process that involves several liver cell types including hepatic stellate cells and Kupffer cells. In addition, recent evidence indicates that bile duct epithelial cells (i.e. cholangiocytes) also participate in the progression of biliary fibrosis that is observed during chronic cholestatic liver diseases, such as primary sclerosing cholangitis. To date, there are no effective treatments for hepatic fibrosis. Several recent studies have demonstrated that the renin-angiotensin system (RAS) plays a key role in hepatic fibrosis. Therapies targeting the RAS may represent a promising paradigm for the prevention and treatment of hepatic fibrosis in the setting of chronic liver disease. In this review, we provide a comprehensive update on the role of RAS in the pathogenesis of hepatic fibrosis in both animal models and human studies. We will discuss the profibrotic mechanisms activated by the RAS and the cell types involved. Studies that have utilized angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors to modulate the RAS in order to ameliorate hepatic fibrosis will also be discussed. Although the cumulative evidence supports the potential for the use of ARBs and ACE inhibitors as treatment for hepatic fibrosis, extensive studies of the effectiveness of RAS therapeutics are necessary in patients with chronic liver disease.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Scott & White Hospital and Texas A&M Health Science Center, College of Medicine, Temple, 76504, USA.
authors.forename: M Kamruzzman
authors.initials: MK
authors.lastname: Munshi
authors.forename: Mohammad N
authors.initials: MN
authors.lastname: Uddin
authors.forename: Shannon S
authors.initials: SS
authors.lastname: Glaser
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors