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. 2007;7:113–134. doi: 10.1007/978-1-4020-6372-5_6

The Role of the Renin-Angiotensin System in Hepatic Fibrosis

JS Lubel 4, FJ Warner 5, PW Angus 4
Editor: Po Sing Leung*
PMCID: PMC7121340

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References

  1. Admiraal PJ, Derkx FH, Danser AH, Pieterman H, Schalekamp MA. Metabolism and production of angiotensin I in different vascular beds in subjects with hypertension. Hypertension. 1990;15(1):44–55. doi: 10.1161/01.hyp.15.1.44. [DOI] [PubMed] [Google Scholar]
  2. Ardaillou R. Active fragments of angiotensin II: enzymatic pathways of synthesis and biological effects. Curr Opin Nephrol Hypertens. 1997;6(1):28–34. doi: 10.1097/00041552-199701000-00006. [DOI] [PubMed] [Google Scholar]
  3. Arroyo V, Bosch J, Mauri M, Viver J, Mas A, Rivera F, Rodes J. Renin, aldosterone and renal haemodynamics in cirrhosis with ascites. Eur J Clin Invest. 1979;9(1):69–73. doi: 10.1111/j.1365-2362.1979.tb01669.x. [DOI] [PubMed] [Google Scholar]
  4. Arthur MJ. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2000;279(2):G245–9. doi: 10.1152/ajpgi.2000.279.2.G245. [DOI] [PubMed] [Google Scholar]
  5. Asbert M, Jimenez W, Gaya J, Gines P, Arroyo V, Rivera F, Rodes J. Assessment of the renin-angiotensin system in cirrhotic patients. Comparison between plasma renin activity and direct measurement of immunoreactive renin. J Hepatol. 1992;15(1-2):179–83. doi: 10.1016/0168-8278(92)90033-l. [DOI] [PubMed] [Google Scholar]
  6. Basso N, Terragno NA. History about the discovery of the renin-angiotensin system. Hypertension. 2001;38(6):1246–9. doi: 10.1161/hy1201.101214. [DOI] [PubMed] [Google Scholar]
  7. Bataller R, Gabele E, Parsons CJ, Morris T, Yang L, Schoonhoven R, Brenner DA, Rippe RA. Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct-ligated rats. Hepatology. 2005;41(5):1046–55. doi: 10.1002/hep.20665. [DOI] [PubMed] [Google Scholar]
  8. Bataller R, Gines P, Nicolas JM, Gorbig MN, Garcia-Ramallo E, Gasull X, Bosch J, Arroyo V, Rodes J. Angiotensin II induces contraction and proliferation of human hepatic stellate cells. Gastroenterology. 2000;118(6):1149–56. doi: 10.1016/s0016-5085(00)70368-4. [DOI] [PubMed] [Google Scholar]
  9. Bataller R, Sancho-Bru P, Gines P, Brenner DA. Liver fibrogenesis: a new role for the renin-angiotensin system. Antioxid Redox Signal. 2005;7(9-10):1346–55. doi: 10.1089/ars.2005.7.1346. [DOI] [PubMed] [Google Scholar]
  10. Bataller R, Sancho-Bru P, Gines P, Lora JM, Al-Garawi A, Sole M, Colmenero J, Nicolas JM, Jimenez W, Weich N, Gutierrez-Ramos JC, Arroyo V, Rodes J. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003;125(1):117–25. doi: 10.1016/s0016-5085(03)00695-4. [DOI] [PubMed] [Google Scholar]
  11. Bataller R, Schwabe RF, Choi YH, Yang L, Paik YH, Lindquist J, Qian T, Schoonhoven R, Hagedorn CH, Lemasters JJ, Brenner DA. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest. 2003;112(9):1383–94. doi: 10.1172/JCI18212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Benter IF, Ferrario CM, Morris M, Diz DI. Antihypertensive actions of angiotensin-(1-7) in spontaneously hypertensive rats. Am J Physiol. 1995;269(1 Pt 2):H313–9. doi: 10.1152/ajpheart.1995.269.1.H313. [DOI] [PubMed] [Google Scholar]
  13. Bosch J, Arroyo V, Betriu A, Mas A, Carrilho F, Rivera F, Navarro-Lopez F, Rodes J. Hepatic hemodynamics and the renin-angiotensin-aldosterone system in cirrhosis. Gastroenterology. 1980;78(1):92–9. [PubMed] [Google Scholar]
  14. Brasier AR, Li J, Copland A. Transcription factors modulating angiotensinogen gene expression in hepatocytes. Kidney Int. 1994;46(6):1564–6. doi: 10.1038/ki.1994.447. [DOI] [PubMed] [Google Scholar]
  15. Brosnihan KB, Li P, Ferrario CM. Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension. 1996;27(3 Pt 2):523–8. doi: 10.1161/01.hyp.27.3.523. [DOI] [PubMed] [Google Scholar]
  16. Burrell LM, Johnston CI, Tikellis C, Cooper ME. ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab. 2004;15(4):166–9. doi: 10.1016/j.tem.2004.03.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Cassiman D, Roskams T. Beauty is in the eye of the beholder: emerging concepts and pitfalls in hepatic stellate cell research. J Hepatol. 2002;37(4):527–35. doi: 10.1016/s0168-8278(02)00263-5. [DOI] [PubMed] [Google Scholar]
  18. Castro CH, Santos RA, Ferreira AJ, Bader M, Alenina N, Almeida AP. Evidence for a functional interaction of the angiotensin-(1-7) receptor Mas with AT1 and AT2 receptors in the mouse heart. Hypertension. 2005;46(4):937–42. doi: 10.1161/01.HYP.0000175813.04375.8a. [DOI] [PubMed] [Google Scholar]
  19. Collister JP, Hendel MD. The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats. J Renin Angiotensin Aldosterone Syst. 2003;4(3):176–9. doi: 10.3317/jraas.2003.028. [DOI] [PubMed] [Google Scholar]
  20. Corpechot C, Barbu V, Wendum D, Kinnman N, Rey C, Poupon R, Housset C, Rosmorduc O. Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology. 2002;35(5):1010–21. doi: 10.1053/jhep.2002.32524. [DOI] [PubMed] [Google Scholar]
  21. Croquet V, Moal F, Veal N, Wang J, Oberti F, Roux J, Vuillemin E, Gallois Y, Douay O, Chappard D, Cales P. Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension. J Hepatol. 2002;37(6):773–80. doi: 10.1016/s0168-8278(02)00307-0. [DOI] [PubMed] [Google Scholar]
  22. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87(5):E1–9. doi: 10.1161/01.res.87.5.e1. [DOI] [PubMed] [Google Scholar]
  23. Enomoto N, Ikejima K, Bradford BU, Rivera CA, Kono H, Goto M, Yamashina S, Schemmer P, Kitamura T, Oide H, Takei Y, Hirose M, Shimizu H, Miyazaki A, Brenner DA, Sato N, Thurman RG. Role of Kupffer cells and gut-derived endotoxins in alcoholic liver injury. J Gastroenterol Hepatol. 2000;15 Suppl:D20–5. doi: 10.1046/j.1440-1746.2000.02179.x. [DOI] [PubMed] [Google Scholar]
  24. Fernandes L, Fortes ZB, Nigro D, Tostes RC, Santos RA, Catelli De, Carvalho MH. Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo. Hypertension. 2001;37(2 Part 2):703–9. doi: 10.1161/01.hyp.37.2.703. [DOI] [PubMed] [Google Scholar]
  25. Ferrario CM. Commentary on Tikellis et al: There is more to discover about angiotensin-converting enzyme. Hypertension. 2003;41(3):390–1. doi: 10.1161/01.HYP.0000060688.57053.7E. [DOI] [PubMed] [Google Scholar]
  26. Ferreira AJ, Santos RA, Almeida AP. Angiotensin-(1-7): cardioprotective effect in myocardial ischemia/reperfusion. Hypertension. 2001;38(3 Pt 2):665–8. doi: 10.1161/01.hyp.38.3.665. [DOI] [PubMed] [Google Scholar]
  27. Ferreira AJ, Santos RA, Almeida AP. Angiotensin-(1-7) improves the post-ischemic function in isolated perfused rat hearts. Braz J Med Biol Res. 2002;35(9):1083–90. doi: 10.1590/s0100-879x2002000900009. [DOI] [PubMed] [Google Scholar]
  28. Freeman EJ, Chisolm GM, Ferrario CM, Tallant EA. Angiotensin-(1-7) inhibits vascular smooth muscle cell growth. Hypertension. 1996;28(1):104–8. doi: 10.1161/01.hyp.28.1.104. [DOI] [PubMed] [Google Scholar]
  29. Friedman SL, Maher JJ, Bissell DM. Mechanisms and therapy of hepatic fibrosis: report of the AASLD Single Topic Basic Research Conference. Hepatology. 2000;32(6):1403–8. doi: 10.1053/jhep.2000.20243. [DOI] [PubMed] [Google Scholar]
  30. Gorelik G, Carbini LA, Scicli AG. Angiotensin 1-7 induces bradykinin-mediated relaxation in porcine coronary artery. J Pharmacol Exp Ther. 1998;286(1):403–10. [PubMed] [Google Scholar]
  31. Grobe JL, Mecca AP, Lingis M, Shenoy V, Bolton TA, Machado JM, Speth RC, Raizada MK and Katovich M 2006 Prevention of Angiotensin II-Induced Cardiac Remodeling by Angiotensin-(1-7) Am J Physiol Heart Circ Physiol [DOI] [PubMed]
  32. Grobe JL, Mecca AP, Mao H, Katovich MJ. Chronic angiotensin-(1-7) prevents cardiac fibrosis in DOCA-salt model of hypertension. Am J Physiol Heart Circ Physiol. 2006;290(6):H2417–23. doi: 10.1152/ajpheart.01170.2005. [DOI] [PubMed] [Google Scholar]
  33. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE 2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–7. doi: 10.1002/path.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002;532(1-2):107–10. doi: 10.1016/s0014-5793(02)03640-2. [DOI] [PubMed] [Google Scholar]
  35. Herath CB, Warner FJ, Lubel JS, Dean R, Lew RA, Smith AI, Burrell LM, Angus PW. The balance between hepatic ACE2 and ACE determines plasma levels of vasodilator peptide angiotensin (1-7) in experimental biliary fibrosis. Journal of Gastroenterology and Hepatology. 2006;21(Suppl. 4):A325. [Google Scholar]
  36. Ikura Y, Ohsawa M, Shirai N, Sugama Y, Fukushima H, Suekane T, Hirayama M, Ehara S, Naruko T, Ueda M. Expression of angiotensin II type 1 receptor in human cirrhotic livers: Its relation to fibrosis and portal hypertension. Hepatol Res. 2005;32(2):107–16. doi: 10.1016/j.hepres.2005.01.017. [DOI] [PubMed] [Google Scholar]
  37. Iwata M, Cowling RT, Gurantz D, Moore C, Zhang S, Yuan JX, Greenberg BH. Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects. Am J Physiol Heart Circ Physiol. 2005;289(6):H2356–63. doi: 10.1152/ajpheart.00317.2005. [DOI] [PubMed] [Google Scholar]
  38. Iyer SN, Ferrario CM, Chappell MC. Angiotensin-(1-7) contributes to the antihypertensive effects of blockade of the renin-angiotensin system. Hypertension. 1998;31(1 Pt 2):356–61. doi: 10.1161/01.hyp.31.1.356. [DOI] [PubMed] [Google Scholar]
  39. Iyer SN, Yamada K, Diz DI, Ferrario CM, Chappell MC. Evidence that prostaglandins mediate the antihypertensive actions of angiotensin-(1-7) during chronic blockade of the renin-angiotensin system. J Cardiovasc Pharmacol. 2000;36(1):109–17. doi: 10.1097/00005344-200007000-00015. [DOI] [PubMed] [Google Scholar]
  40. Jamaluddin M, Meng T, Sun J, Boldogh I, Han Y, Brasier AR. Angiotensin II induces nuclear factor (NF)-kappaB1 isoforms to bind the angiotensinogen gene acute-phase response element: a stimulus-specific pathway for NF-kappaB activation. Mol Endocrinol. 2000;14(1):99–113. doi: 10.1210/mend.14.1.0400. [DOI] [PubMed] [Google Scholar]
  41. Jonsson JR, Clouston AD, Ando Y, Kelemen LI, Horn MJ, Adamson MD, Purdie DM, Powell EE. Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology. 2001;121(1):148–55. doi: 10.1053/gast.2001.25480. [DOI] [PubMed] [Google Scholar]
  42. Kallis Y, Alison MR and Forbes SJ 2006 Bone marrow stem cells and liver disease Gut [DOI] [PMC free article] [PubMed]
  43. Kanno K, Tazuma S, Chayama K. AT1A-deficient mice show less severe progression of liver fibrosis induced by CCl(4) Biochem Biophys Res Commun. 2003;308(1):177–83. doi: 10.1016/s0006-291x(03)01357-3. [DOI] [PubMed] [Google Scholar]
  44. Kanno K, Tazuma S, Nishioka T, Hyogo H, Chayama K. Angiotensin II participates in hepatic inflammation and fibrosis through MCP-1 expression. Dig Dis Sci. 2005;50(5):942–8. doi: 10.1007/s10620-005-2669-7. [DOI] [PubMed] [Google Scholar]
  45. Knittel T, Mehde M, Kobold D, Saile B, Dinter C, Ramadori G. Expression patterns of matrix metalloproteinases and their inhibitors in parenchymal and non-parenchymal cells of rat liver: regulation by TNF-alpha and TGF-beta1. J Hepatol. 1999;30(1):48–60. doi: 10.1016/s0168-8278(99)80007-5. [DOI] [PubMed] [Google Scholar]
  46. Kojima H, Tsujimoto T, Uemura M, Takaya A, Okamoto S, Ueda S, Nishio K, Miyamoto S, Kubo A, Minamino N, Kangawa K, Matsuo H, Fukui H. Significance of increased plasma adrenomedullin concentration in patients with cirrhosis. J Hepatol. 1998;28(5):840–6. doi: 10.1016/s0168-8278(98)80235-3. [DOI] [PubMed] [Google Scholar]
  47. Kono H, Rusyn I, Yin M, Gabele E, Yamashina S, Dikalova A, Kadiiska MB, Connor HD, Mason RP, Segal BH, Bradford BU, Holland SM, Thurman RG. NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease. J Clin Invest. 2000;106(7):867–72. doi: 10.1172/JCI9020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Kostenis E, Milligan G, Christopoulos A, Sanchez-Ferrer CF, Heringer-Walther S, Sexton PM, Gembardt F, Kellett E, Martini L, Vanderheyden P, Schultheiss HP, Walther T. G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor. Circulation. 2005;111(14):1806–13. doi: 10.1161/01.CIR.0000160867.23556.7D. [DOI] [PubMed] [Google Scholar]
  49. Kucharewicz I, Chabielska E, Pawlak D, Matys T, Rolkowski R, Buczko W. The antithrombotic effect of angiotensin-(1-7) closely resembles that of losartan. J Renin Angiotensin Aldosterone Syst. 2000;1(3):268–72. doi: 10.3317/jraas.2000.041. [DOI] [PubMed] [Google Scholar]
  50. Kucharewicz I, Pawlak R, Matys T, Pawlak D, Buczko W. Antithrombotic effect of captopril and losartan is mediated by angiotensin-(1-7) Hypertension. 2002;40(5):774–9. doi: 10.1161/01.hyp.0000035396.27909.40. [DOI] [PubMed] [Google Scholar]
  51. Kurikawa N, Suga M, Kuroda S, Yamada K, Ishikawa H. An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells. Br J Pharmacol. 2003;139(6):1085–94. doi: 10.1038/sj.bjp.0705339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Lambert DW, Yarski M, Warner FJ, Thornhill P, Parkin ET, Smith AI, Hooper NM, Turner AJ. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2) J Biol Chem. 2005;280(34):30113–9. doi: 10.1074/jbc.M505111200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Leung PS, Chappell MC. A local pancreatic renin-angiotensin system: endocrine and exocrine roles. Int J Biochem Cell Biol. 2003;35(6):838–46. doi: 10.1016/s1357-2725(02)00179-6. [DOI] [PubMed] [Google Scholar]
  54. Leung PS, Suen PM, Ip SP, Yip CK, Chen G, Lai PB. Expression and localization of AT1 receptors in hepatic Kupffer cells: its potential role in regulating a fibrogenic response. Regul Pept. 2003;116(1-3):61–9. doi: 10.1016/s0167-0115(03)00192-7. [DOI] [PubMed] [Google Scholar]
  55. Lew RA, Warner FJ, Hanchapola I, Smith AI. Characterization of angiotensin converting enzyme-2 (ACE2) in human urine. International Journal Of Peptide Research And Therapeutics. 2006;12(3):283–289. doi: 10.1007/s10989-006-9031-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Li P, Chappell MC, Ferrario CM, Brosnihan KB. Angiotensin-(1-7) augments bradykinin-induced vasodilation by competing with ACE and releasing nitric oxide. Hypertension. 1997;29(1 Pt 2):394–400. doi: 10.1161/01.hyp.29.1.394. [DOI] [PubMed] [Google Scholar]
  57. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–4. doi: 10.1038/nature02145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Li X, Meng Y, Yang XS, Zhang ZS, Wu PS, Zou JL. [Perindopril attenuates the progression of CCl4-inducing rat hepatic fibrosis] Zhonghua Gan Zang Bing Za Zhi. 2004;12(1):32–4. [PubMed] [Google Scholar]
  59. Li X, Meng Y, Zhang ZS, Yang XS, Wu PS. [Effect of ACE-I and AT-1 receptor blocker on the progression of CCl(4)-inducing rat hepatic fibrogenesis] Zhonghua Yi Xue Za Zhi. 2003;83(14):1241–5. [PubMed] [Google Scholar]
  60. Lodato F, Mazzella G, Festi D, Azzaroli F, Colecchia A, Roda E. Hepatocellular carcinoma prevention: A worldwide emergence between the opulence of developed countries and the economic constraints of developing nations. World J Gastroenterol. 2006;12(45):7239–49. doi: 10.3748/wjg.v12.i45.7239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Lubel JS, Herath CB, Warner FJ, Jia ZY, Burrell LM, Angus PW. Upregulation of the ACE2/Ang(1-7)/Mas receptor axis in the bile duct ligation (BDL) model of hepatic fibrosis does not affect hepatic sinusoidal resistance. Journal of Gastroenterology and Hepatology. 2006;21(Suppl 4):A332. [Google Scholar]
  62. Marra F, DeFranco R, Grappone C, Milani S, Pastacaldi S, Pinzani M, Romanelli RG, Laffi G, Gentilini P. Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: correlation with monocyte infiltration. Am J Pathol. 1998;152(2):423–30. [PMC free article] [PubMed] [Google Scholar]
  63. McAllister-Lucas LM, Ruland J, Siu K, Jin X, Gu S, Kim DS, Kuffa P, Kohrt D, Mak TW, Nunez G and Lucas PC 2006 CARMA3/Bcl10/MALT1-dependent NF-{kappa}B activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells Proc Natl Acad Sci U S A [DOI] [PMC free article] [PubMed]
  64. Miyoshi M, Nagata K, Imoto T, Goto O, Ishida A, Watanabe T. ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats. Am J Physiol Regul Integr Comp Physiol. 2003;284(4):R1092–7. doi: 10.1152/ajpregu.00700.2002. [DOI] [PubMed] [Google Scholar]
  65. Morris BJ, Iwamoto HS, Reid IA. Localization of angiotensinogen in rat liver by immunocytochemistry. Endocrinology. 1979;105(3):796–800. doi: 10.1210/endo-105-3-796. [DOI] [PubMed] [Google Scholar]
  66. Nabeshima Y, Tazuma S, Kanno K, Hyogo H, Iwai M, Horiuchi M, Chayama K. Anti-fibrogenic function of angiotensin II type 2 receptor in CCl4-induced liver fibrosis. Biochem Biophys Res Commun. 2006;346(3):658–64. doi: 10.1016/j.bbrc.2006.05.183. [DOI] [PubMed] [Google Scholar]
  67. Nakamoto H, Ferrario CM, Fuller SB, Robaczewski DL, Winicov E, Dean RH. Angiotensin-(1-7) and nitric oxide interaction in renovascular hypertension. Hypertension. 1995;25(4 Pt 2):796–802. doi: 10.1161/01.hyp.25.4.796. [DOI] [PubMed] [Google Scholar]
  68. Ocaranza MP, Godoy I, Jalil JE, Varas M, Collantes P, Pinto M, Roman M, Ramirez C, Copaja M, Diaz-Araya G, Castro P, Lavandero S. Enalapril attenuates downregulation of Angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat. Hypertension. 2006;48(4):572–8. doi: 10.1161/01.HYP.0000237862.94083.45. [DOI] [PubMed] [Google Scholar]
  69. Ohishi T, Saito H, Tsusaka K, Toda K, Inagaki H, Hamada Y, Kumagai N, Atsukawa K, Ishii H. Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats. Hepatol Res. 2001;21(2):147–158. doi: 10.1016/s1386-6346(01)00102-4. [DOI] [PubMed] [Google Scholar]
  70. Paizis G, Cooper ME, Schembri JM, Tikellis C, Burrell LM, Angus PW. Up-regulation of components of the renin-angiotensin system in the bile duct-ligated rat liver. Gastroenterology. 2002;123(5):1667–76. doi: 10.1053/gast.2002.36561. [DOI] [PubMed] [Google Scholar]
  71. Paizis G, Gilbert RE, Cooper ME, Murthi P, Schembri JM, Wu LL, Rumble JR, Kelly DJ, Tikellis C, Cox A, Smallwood RA, Angus PW. Effect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis. J Hepatol. 2001;35(3):376–85. doi: 10.1016/s0168-8278(01)00146-5. [DOI] [PubMed] [Google Scholar]
  72. Paizis G, Tikellis C, Cooper ME, Schembri JM, Lew RA, Smith AI, Shaw T, Warner FJ, Zuilli A, Burrell LM, Angus PW. Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut. 2005;54(12):1790–6. doi: 10.1136/gut.2004.062398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Pereira RM, Dos Santos RA, Teixeira MM, Leite VH, Costa LP, da Costa Dias FL, Barcelos LS, Collares GB and Simoes ESAC 2006 The renin-angiotensin system in a rat model of hepatic fibrosis: Evidence for a protective role of Angiotensin-(1-7) J Hepatol [DOI] [PubMed]
  74. Ramalho LN, Ramalho FS, Zucoloto S, Castro-e-Silva Junior O, Correa FM, Elias Junior J, Magalhaes JF. Effect of losartan, an angiotensin II antagonist, on secondary biliary cirrhosis. Hepatogastroenterology. 2002;49(48):1499–502. [PubMed] [Google Scholar]
  75. Ramos SG, Montenegro AP, Goissis G, Rossi MA. Captopril reduces collagen and mast cell and eosinophil accumulation in pig serum-induced rat liver fibrosis. Pathol Int. 1994;44(9):655–61. doi: 10.1111/j.1440-1827.1994.tb02944.x. [DOI] [PubMed] [Google Scholar]
  76. Rice GI, Jones AL, Grant PJ, Carter AM, Turner AJ, Hooper NM. Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study. Hypertension. 2006;48(5):914–20. doi: 10.1161/01.HYP.0000244543.91937.79. [DOI] [PubMed] [Google Scholar]
  77. Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004;383(Pt 1):45–51. doi: 10.1042/BJ20040634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Richoux JP, Cordonnier JL, Bouhnik J, Clauser E, Corvol P, Menard J, Grignon G. Immunocytochemical localization of angiotensinogen in rat liver and kidney. Cell Tissue Res. 1983;233(2):439–51. doi: 10.1007/BF00238309. [DOI] [PubMed] [Google Scholar]
  79. Rimola A, Londono MC, Guevara G, Bruguera M, Navasa M, Forns X, Garcia-Retortillo M, Garcia-Valdecasas JC, Rodes J. Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation. Transplantation. 2004;78(5):686–91. doi: 10.1097/01.tp.0000128913.09774.ce. [DOI] [PubMed] [Google Scholar]
  80. Rincon-Sanchez AR, Covarrubias A, Rivas-Estilla AM, Pedraza-Chaverri J, Cruz C, Islas-Carbajal MC, Panduro A, Estanes A, Armendariz-Borunda J. PGE2 alleviates kidney and liver damage, decreases plasma renin activity and acute phase response in cirrhotic rats with acute liver damage. Exp Toxicol Pathol. 2005;56(4-5):291–303. doi: 10.1016/j.etp.2004.10.003. [DOI] [PubMed] [Google Scholar]
  81. Rivera-Huizar S, Rincon-Sanchez AR, Covarrubias-Pinedo A, Islas-Carbajal MC, Gabriel-Ortiz G, Pedraza-Chaverri J, Alvarez-Rodriguez A, Meza-Garcia E, Armendariz-Borunda J. Renal dysfunction as a consequence of acute liver damage by bile duct ligation in cirrhotic rats. Exp Toxicol Pathol. 2006;58(2-3):185–95. doi: 10.1016/j.etp.2006.05.001. [DOI] [PubMed] [Google Scholar]
  82. Ron D, Brasier AR, Habener JF. Transcriptional regulation of hepatic angiotensinogen gene expression by the acute-phase response. Mol Cell Endocrinol. 1990;74(3):C97–104. doi: 10.1016/0303-7207(90)90221-s. [DOI] [PubMed] [Google Scholar]
  83. Russo FP, Alison MR, Bigger BW, Amofah E, Florou A, Amin F, Bou-Gharios G, Jeffery R, Iredale JP, Forbes SJ. The bone marrow functionally contributes to liver fibrosis. Gastroenterology. 2006;130(6):1807–21. doi: 10.1053/j.gastro.2006.01.036. [DOI] [PubMed] [Google Scholar]
  84. Sakata T, Takenaga N, Endoh T, Wada O, Matsuki K. Diagnostic significance of serum angiotensin-converting enzyme activity in biochemical tests with special reference of chronic liver diseases. Jpn J Med. 1991;30(5):402–7. doi: 10.2169/internalmedicine1962.30.402. [DOI] [PubMed] [Google Scholar]
  85. Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100(14):8258–63. doi: 10.1073/pnas.1432869100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Sasaki K, Taniguchi M, Miyoshi M, Goto O, Sato K, Watanabe T. Are transcription factors NF-kappaB and AP-1 involved in the ANG II-stimulated production of proinflammatory cytokines induced by LPS in dehydrated rats? Am J Physiol Regul Integr Comp Physiol. 2005;289(6):R1599–608. doi: 10.1152/ajpregu.00124.2005. [DOI] [PubMed] [Google Scholar]
  87. Sawa H. [Angiotensinogen: gene expression and protein localization in human tissues] Hokkaido Igaku Zasshi. 1990;65(2):189–99. [PubMed] [Google Scholar]
  88. Schiavone MT, Santos RA, Brosnihan KB, Khosla MC, Ferrario CM. Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide. Proc Natl Acad Sci U S A. 1988;85(11):4095–8. doi: 10.1073/pnas.85.11.4095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Schuppan D, Ruehl M, Somasundaram R, Hahn EG. Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis. 2001;21(3):351–72. doi: 10.1055/s-2001-17556. [DOI] [PubMed] [Google Scholar]
  90. Sewnath ME, van der Poll T, van Noorden CJ, ten Kate FJ, Gouma DJ. Cholestatic interleukin-6-deficient mice succumb to endotoxin-induced liver injury and pulmonary inflammation. Am J Respir Crit Care Med. 2004;169(3):413–20. doi: 10.1164/rccm.200303-311OC. [DOI] [PubMed] [Google Scholar]
  91. Silva DM, Vianna HR, Cortes SF, Campagnole-Santos MJ, Santos RA and Lemos VS 2006 Evidence for a new angiotensin-(1-7) receptor subtype in the aorta of Sprague-Dawley rats Peptides [DOI] [PubMed]
  92. Strawn WB, Ferrario CM, Tallant EA. Angiotensin-(1-7) reduces smooth muscle growth after vascular injury. Hypertension. 1999;33(1 Pt 2):207–11. doi: 10.1161/01.hyp.33.1.207. [DOI] [PubMed] [Google Scholar]
  93. Tallant EA, Ferrario CM, Gallagher PE. Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am J Physiol Heart Circ Physiol. 2005;289(4):H1560–6. doi: 10.1152/ajpheart.00941.2004. [DOI] [PubMed] [Google Scholar]
  94. Thomas MC, Tikellis C. ACE2; an ACE up the Sleeve. Current enzyme inhibition. 2005;1:51–63. [Google Scholar]
  95. Tigerstedt RBP. Niere und Kreislauf. Skand Arch Physiol. 1898;8:223–271. [Google Scholar]
  96. Timmermans PB, Benfield P, Chiu AT, Herblin WF, Wong PC, Smith RD. Angiotensin II receptors and functional correlates. Am J Hypertens. 1992;5(12 Pt 2):221S–235S. doi: 10.1093/ajh/5.12.221s. [DOI] [PubMed] [Google Scholar]
  97. Timmermans PB, Chiu AT, Herblin WF, Wong PC, Smith RD. Angiotensin II receptor subtypes. Am J Hypertens. 1992;5(6 Pt 1):406–10. doi: 10.1093/ajh/5.6.406. [DOI] [PubMed] [Google Scholar]
  98. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275(43):33238–43. doi: 10.1074/jbc.M002615200. [DOI] [PubMed] [Google Scholar]
  99. Toblli JE, Ferder L, Stella I, Angerosa M, Inserra F. Enalapril prevents fatty liver in nephrotic rats. J Nephrol. 2002;15(4):358–67. [PubMed] [Google Scholar]
  100. Tuncer I, Ozbek H, Ugras S, Bayram I. Anti-fibrogenic effects of captopril and candesartan cilexetil on the hepatic fibrosis development in rat. The effect of AT1-R blocker on the hepatic fibrosis. Exp Toxicol Pathol. 2003;55(2-3):159–66. doi: 10.1078/0940-2993-00309. [DOI] [PubMed] [Google Scholar]
  101. Turner AJ. Exploring the structure and function of zinc metallopeptidases: old enzymesnew discoveries. Biochem Soc Trans. 2003;31(Pt 3):723–7. doi: 10.1042/bst0310723. [DOI] [PubMed] [Google Scholar]
  102. Ueda S, Masumori-Maemoto S, Wada A, Ishii M, Brosnihan KB, Umemura S. Angiotensin(1-7) potentiates bradykinin-induced vasodilatation in man. J Hypertens. 2001;19(11):2001–9. doi: 10.1097/00004872-200111000-00010. [DOI] [PubMed] [Google Scholar]
  103. Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, Godbout K, Parsons T, Baronas E, Hsieh F, Acton S, Patane M, Nichols A, Tummino P. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002;277(17):14838–43. doi: 10.1074/jbc.M200581200. [DOI] [PubMed] [Google Scholar]
  104. Vlachogiannakos J, Tang AK, Patch D, Burroughs AK. Angiotensin converting enzyme inhibitors and angiotensin II antagonists as therapy in chronic liver disease. Gut. 2001;49(2):303–8. doi: 10.1136/gut.49.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. von Bohlen und, Halbach O. Angiotensin IV in the central nervous system. Cell Tissue Res. 2003;311(1):1–9. doi: 10.1007/s00441-002-0655-3. [DOI] [PubMed] [Google Scholar]
  106. Walters PE, Gaspari TA, Widdop RE. Angiotensin-(1-7) acts as a vasodepressor agent via angiotensin II type 2 receptors in conscious rats. Hypertension. 2005;45(5):960–6. doi: 10.1161/01.HYP.0000160325.59323.b8. [DOI] [PubMed] [Google Scholar]
  107. Wang XZ, Zhang LJ, Li D, Huang YH, Chen ZX, Li B. Effects of transmitters and interleukin-10 on rat hepatic fibrosis induced by CCl4. World J Gastroenterol. 2003;9(3):539–43. doi: 10.3748/wjg.v9.i3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Warner FJ, Lew RA, Smith AI, Lambert DW, Hooper NM, Turner AJ. Angiotensin-converting enzyme 2 (ACE2), but not ACE, is preferentially localized to the apical surface of polarized kidney cells. J Biol Chem. 2005;280(47):39353–62. doi: 10.1074/jbc.M508914200. [DOI] [PubMed] [Google Scholar]
  109. Warner FJ, Smith AI, Hooper NM, Turner AJ. Angiotensin-converting enzyme-2: a molecular and cellular perspective. Cell Mol Life Sci. 2004;61(21):2704–13. doi: 10.1007/s00018-004-4240-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Wei H, Li D, Lu H, Zhan Y, Wang Z, Huang X, Pan Q, Xu Q. Effects of angiotensin II receptor blockade on hepatic fibrosis in rats. Zhonghua Gan Zang Bing Za Zhi. 2000;8(5):302–4. [PubMed] [Google Scholar]
  111. Wei HS, Lu HM, Li DG, Zhan YT, Wang ZR, Huang X, Cheng JL, Xu QF. The regulatory role of AT 1 receptor on activated HSCs in hepatic fibrogenesis:effects of RAS inhibitors on hepatic fibrosis induced by CCl(4) World J Gastroenterol. 2000;6(6):824–828. doi: 10.3748/wjg.v6.i6.824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Wei YH, Jun L, Qiang CJ. Effect of losartan, an angiotensin II antagonist on hepatic fibrosis induced by CCl4 in rats. Dig Dis Sci. 2004;49(10):1589–94. doi: 10.1023/b:ddas.0000043369.88701.5b. [DOI] [PubMed] [Google Scholar]
  113. Whalen R, Rockey DC, Friedman SL, Boyer TD. Activation of rat hepatic stellate cells leads to loss of glutathione S-transferases and their enzymatic activity against products of oxidative stress. Hepatology. 1999;30(4):927–33. doi: 10.1002/hep.510300404. [DOI] [PubMed] [Google Scholar]
  114. Yang L, Bataller R, Dulyx J, Coffman TM, Gines P, Rippe RA, Brenner DA. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol. 2005;43(2):317–23. doi: 10.1016/j.jhep.2005.02.034. [DOI] [PubMed] [Google Scholar]
  115. Yokohama S, Tokusashi Y, Nakamura K, Tamaki Y, Okamoto S, Okada M, Aso K, Hasegawa T, Aoshima M, Miyokawa N, Haneda M, Yoneda M. Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis. World J Gastroenterol. 2006;12(2):322–6. doi: 10.3748/wjg.v12.i2.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Yokohama S, Yoneda M, Haneda M, Okamoto S, Okada M, Aso K, Hasegawa T, Tokusashi Y, Miyokawa N, Nakamura K. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology. 2004;40(5):1222–5. doi: 10.1002/hep.20420. [DOI] [PubMed] [Google Scholar]
  117. Yoshiji H, Kuriyama S, Fukui H. Angiotensin-I-converting enzyme inhibitors may be an alternative anti-angiogenic strategy in the treatment of liver fibrosis and hepatocellular carcinoma. Possible role of vascular endothelial growth factor. Tumour Biol. 2002;23(6):348–56. doi: 10.1159/000069792. [DOI] [PubMed] [Google Scholar]
  118. Yoshiji H, Kuriyama S, Kawata M, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Fukui H. The angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth and angiogenesis: possible role of the vascular endothelial growth factor. Clin Cancer Res. 2001;7(4):1073–8. [PubMed] [Google Scholar]
  119. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Fukui H. Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology. 2001;34(4 Pt 1):745–50. doi: 10.1053/jhep.2001.28231. [DOI] [PubMed] [Google Scholar]
  120. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Yanase K, Namisaki T, Yamazaki M, Tsujinoue H, Imazu H, Fukui H. Angiotensin-II induces the tissue inhibitor of metalloproteinases-1 through the protein kinase-C signaling pathway in rat liver fibrosis development. Hepatol Res. 2003;27(1):51–56. doi: 10.1016/s1386-6346(03)00160-8. [DOI] [PubMed] [Google Scholar]
  121. Yoshiji H, Noguchi R, Fukui H. Combined effect of an ACE inhibitor, perindopril, and interferon on liver fibrosis markers in patients with chronic hepatitis C. J Gastroenterol. 2005;40(2):215–6. doi: 10.1007/s00535-004-1523-6. [DOI] [PubMed] [Google Scholar]
  122. Yoshiji H, Noguchi R, Kuriyama S, Yoshii J, Ikenaka Y. Combination of interferon and angiotensin-converting enzyme inhibitor, perindopril, suppresses liver carcinogenesis and angiogenesis in mice. Oncol Rep. 2005;13(3):491–5. [PubMed] [Google Scholar]
  123. Yoshiji H, Yoshii J, Ikenaka Y, Noguchi R, Tsujinoue H, Nakatani T, Imazu H, Yanase K, Kuriyama S, Fukui H. Inhibition of renin-angiotensin system attenuates liver enzyme-altered preneoplastic lesions and fibrosis development in rats. J Hepatol. 2002;37(1):22–30. doi: 10.1016/s0168-8278(02)00104-6. [DOI] [PubMed] [Google Scholar]
  124. Yoshiji H, Yoshii J, Ikenaka Y, Noguchi R, Yanase K, Tsujinoue H, Imazu H, Fukui H. Suppression of the renin-angiotensin system attenuates vascular endothelial growth factor-mediated tumor development and angiogenesis in murine hepatocellular carcinoma cells. Int J Oncol. 2002;20(6):1227–31. [PubMed] [Google Scholar]
  125. Zhang X, Yu WP, Gao L, Wei KB, Ju JL, Xu JZ. Effects of lipopolysaccharides stimulated Kupffer cells on activation of rat hepatic stellate cells. World J Gastroenterol. 2004;10(4):610–3. doi: 10.3748/wjg.v10.i4.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. Zhang Y, Yang X, Wu P, Xu L, Liao G, Yang G. Expression of angiotensin II type 1 receptor in rat hepatic stellate cells and its effects on cell growth and collagen production. Horm Res. 2003;60(3):105–10. doi: 10.1159/000072520. [DOI] [PubMed] [Google Scholar]
  127. Zhang YJ, Yang XS, Wu PS, Li X, Zhang XF, Chen XQ, Yu ZX. Effects of angiotensin II and losartan on the growth and proliferation of hepatic stellate cells. Di Yi Jun Yi Da Xue Xue Bao. 2003;23(3):219–21. [PubMed] [Google Scholar]
  128. Zisman LS, Keller RS, Weaver B, Lin Q, Speth R, Bristow MR, Canver CC. Increased angiotensin-(1-7)-forming activity in failing human heart ventricles: evidence for upregulation of the angiotensin-converting enzyme Homologue ACE2. Circulation. 2003;108(14):1707–12. doi: 10.1161/01.CIR.0000094734.67990.99. [DOI] [PubMed] [Google Scholar]
  129. Zisman LS, Meixell GE, Bristow MR, Canver CC. Angiotensin-(1-7) formation in the intact human heart: in vivo dependence on angiotensin II as substrate. Circulation. 2003;108(14):1679–81. doi: 10.1161/01.CIR.0000094733.61689.D4. [DOI] [PubMed] [Google Scholar]

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