Angiotensin receptor blockers in the treatment of NASH/NAFLD: Could they be a first-class option?

Advances in Therapy

Volumn 25, Issue 11, 2008, Pages 1141-1174

  Georgescu, Eugen Florin ^a  

^a Filantropia University Hospital   (Romania)

Author keywords

ARBs; Insulin resistance; Metabolic syndrome; Nonalcoholic fatty liver disease; Renin angiotensin system; Steatohepatitis

Indexed keywords

ANGIOTENSIN 1 RECEPTOR ANTAGONIST; BENZIMIDAZOLE DERIVATIVE; BENZOIC ACID DERIVATIVE; CANDESARTAN; LOSARTAN; TELMISARTAN; TETRAZOLE DERIVATIVE;

ANIMAL; DRUG EFFECT; FATTY LIVER; HUMAN; INSULIN RESISTANCE; METABOLIC SYNDROME X; PATHOPHYSIOLOGY; PHYSIOLOGY; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW;

ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS; ANIMALS; BENZIMIDAZOLES; BENZOATES; FATTY LIVER; HUMANS; INSULIN RESISTANCE; LOSARTAN; METABOLIC SYNDROME X; RENIN-ANGIOTENSIN SYSTEM; TETRAZOLES;

EID: 66549124116     PISSN: 0741238X     EISSN: 18658652     Source Type: Journal    
DOI: 10.1007/s12325-008-0110-2     Document Type: Review

References (193)

1. Angulo P. GI epidemiology: nonalcoholic fatty liver disease. Aliment Pharmacol Ter. 2007;25:883-889.
2. Powell EE, Jonsson JR, Clouston AD. Steatosis: co-factor in other liver diseases. Hepatology. 2006;42:5-13.
3. Caldwell SH, Oelsner DH, Iezzoni JC, et al. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999;29:664-669. (Pubitemid 29109578)
4. Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002;123: 134-140. (Pubitemid 34747534)
5. Kleiner DE, Brunt EM, Van Natta M, et al. for the Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;4:1313-1321. (Pubitemid 40770284)
6. Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 2001;21:27-41. (Pubitemid 32240484)
7. Diehl AM. Fatty liver, hypertension, and the metabolic syndrome. Gut. 2004;53:923-924. (Pubitemid 38824145)
8. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37:917-923. (Pubitemid 36397405)
9. Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis. 2001;21:17-26. (Pubitemid 32240483)
10. Mulhall BP, Ong JP, Younossi ZM. Nonalcoholic fatty liver disease: an overview. J Gastroenterol Hepatol. 2002;17:1136-1143. (Pubitemid 36015607)
11. Hilden M, Christofersen P, Juhl E, Dalgaard JB. Liver histology in a "normal" population-examinations of 503 consecutive fatal trafc casualties. Scand J Gastroenterol. 1977;12:593-597. (Pubitemid 8149779)
12. Charlton M, Kasparova P, Weston S, et al. Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl. 2001;7:608-614. (Pubitemid 32677885)
13. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology. 1990;12:1106-1110.
14. Grattagliano I, Portincasa P, Palmieri V, Palasciano G. Managing nonalcoholic fatty liver disease. Recommendations for family physicians. Can Fam Physician. 2007;53:857-863. (Pubitemid 47164278)
15. Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study. Comment in: Am J Gastroenterol. 2003;98:1915-1917.
16. Fassio E, Alvarez E, Domínguez N, et al. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004;40:820-826. (Pubitemid 39288114)
17. Björnsson E. The clinical aspects of nonalcoholic fatty liver disease. Minerva Gastroenterol Dietol. 2008;54:7-18. (Pubitemid 351518566)
18. Neuschwander-Tetri BA. Fatty liver and the metabolic syndrome. Curr Opin Gastroenterol. 2007;3:193-198. (Pubitemid 46192974)
19. Tarantino G, Saldalamacchia G, Conca P, Arena A. Non-alcoholic fatty liver disease: further expression of the metabolic syndrome. J Gastroenterol Hepatol. 2007;22:293-303. (Pubitemid 46238755)
20. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595-1607. (Pubitemid 19004941)
21. Pagano G, Pacini G, Musso G, et al. Nonalcoholic steatohepatitis, insulin resistance, metabolic syndrome: further evidence for an etiologic association. Hepatology. 2002;35:365-372.
22. Day CP, James O F. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998;114:842-845.
23. Lima FB, Ties RS, Garvey WT. Glucose and insulin regulate insulin sensitivity in primary cultured adipocytes without afecting insulin receptor kinase activity. Endocrinology. 1991;128:2415-2426.
24. Zamora-Valdes D, Chavez-Tapia NC, Mendez-Sanchez N. Molecular mechanisms of insulin resistance. Med Sur. 2004;11:149-159.
25. White MF. Insulin signaling in health and disease. Science. 2003;302:1710-1711. (Pubitemid 37505726)
26. Shulman GI. Cellular mechanisms of insulin resistance in humans. Am J Cardiol. 1999;84:3-10.
27. Dupont J, Derouet M, Simon J, Taouis M. Effect of nutritional state on the formation of a complex involving insulin receptor IRS-1, the 52 kDa Src homology/collagen protein (Shc) isoform and phosphatidylinositol 3'-kinase activity. Biochem J. 1998;335:293-300.
28. Sattar AA, Berhanu C, Gebreselassie S, Berhanu P. Human insulin receptor juxtamembrane domain independent insulin signaling. Cell Biol Int. 2007;31:815-824. (Pubitemid 46765140)
29. Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22:153-183. (Pubitemid 32458157)
30. Choi BM, Yoo KH, Bae IS, et al. Angiotensin-converting enzyme inhibition modulates mitogen-activated protein kinase family expressions in the neonatal rat kidney. Pediatr Res. 2005; 57:115-123.
31. Wang X, Martindale JL, Liu Y, Holbrook NJ. The cellular response to oxidative stress: infuences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem J. 1998;333:291-300. (Pubitemid 28379529)
32. Duvnjak M, Lerotic I, Barsic N, et al. Pathogenesis and management issues for non-alcoholic fatty liver disease. World J Gastroenterol. 2007;13:4539-4550. (Pubitemid 47455230)
33. Capeau J, Bastard J P, Vigouroux C. Syndrome metabolique et insulinoresistance: physiopathologie. Mt Cardio. 2006;2:155-164.
34. Méndez-Sánchez N, Arrese M, Zamora-Valdés D, Uribe M. Current concepts in the pathogenesis of nonalcoholic fatty liver disease. Liver Int. 2007;27:423-433. (Pubitemid 46534563)
35. McAvoy NC, Ferguson JW, Campbell IW, Hayes PC. Non-alcoholic fatty liver disease: natural history, pathogenesis and treatment. Br J Diabetes Vasc Dis. 2006;6:251-260. (Pubitemid 46111467)
36. Cusi K, Maezono K, Osman A, et al. Insulin resistance diferentially afects the PI 3-kinase-and MAP kinase-mediated signaling in human muscle. J Clin Invest. 2000;105:311-320. (Pubitemid 30094451)
37. Low Wang CC, Goalstone ML, Draznin B. Molecular mechanisms of insulin resistance that impact cardiovascular biology. Diabetes. 2004;53:2735-2740. (Pubitemid 39425897)
38. Miles JM, Park YS, Walewicz D, et al. Systemic and forearm triglyceride metabolism: fate of lipoprotein lipase-generated glycerol and free fatty acids. Diabetes. 2004;53:521-527. (Pubitemid 38270618)
39. Havel RJ, Hamilton RL. Hepatic catabolism of remnant lipoproteins: where the action is. Arterioscler Tromb Vasc Biol. 2004;24:213-215. (Pubitemid 38197571)
40. Donnelly KL, Smith CI, Schwarzenberg SJ, et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005;115:1343-1351. (Pubitemid 40629054)
41. Tamura S, Shimomura I. Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease. J Clin Invest. 2005;115:1139-1142. (Pubitemid 40629030)
42. Timlin MT, Parks EJ. Temporal pattern of de novo lipogenesis in the postprandial state in healthy men. Am J Clin Nutr. 2005;81:35-42. (Pubitemid 43073373)
43. Schwarz J-M, Linfoot P, Dare D, et al. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr. 2003;77:43-50. (Pubitemid 36015371)
44. Coleman RA, Lee DP. Enzymes of triacylglycerol synthesis and their regulation. Prog Lipid Res. 2004;43:134-176. (Pubitemid 37492937)
45. Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest. 2008;118:829-838 (Pubitemid 351364588)
46. Yamaguchi K, Yang L, McCall S, et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fbrosis in obese mice with nonalcoholic steatohepatitis. Hepatology. 2007;45:1366-1374. (Pubitemid 46918320)
47. Kohli R, Pan X, Malladi P, et al. Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the phosphatidylinositol 3-kinase cell survival pathway. J Biol Chem. 2007;282:21327-21336. (Pubitemid 47099964)
48. Samuel VT, Liu ZX, Qu X, et al. Mechanism of hepatic insulin resistance in nonalcoholic fatty liver disease. J Biol Chem. 2004;279:32345-32353. (Pubitemid 39014687)
49. Samuel VT, Liu ZX, Wang A, et al. Inhibition of protein kinase C epsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J Clin Invest. 2007;117:739-745. (Pubitemid 46348532)
50. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114:147-152. (Pubitemid 39071617)
51. Bergamini CM, Gambetti S, Dondi A, Cervellati C. Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des. 2004;10:1611-1626. (Pubitemid 38559774)
52. Perez-Carreras M, Del Hoyo P, Martín MA, et al. DEffective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology. 2003;38:999-1007. (Pubitemid 37221683)
53. Pan M, Cederbaum AI, Zhang YL, et al. Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production. J Clin Invest. 2004;113:1277-1287. (Pubitemid 39069927)
54. Sugimoto R, Enjoji M, Kohjima M, et al. High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase. Liver Int. 2005;25:1018-1026. (Pubitemid 41404025)
55. Malhi H, Bronk SF, Werneburg N W, Gores GJ. Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J Biol Chem. 2006;281:12093-12101. (Pubitemid 43855473)
56. Van Ginderachter JA, Movahedi K, Van den Bossche J, De Baetselier P. Macrophages, PPARs, and cancer. PPAR Res. 2008;2008:169414.
57. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5:953-964. (Pubitemid 41746764)
58. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175-184. (Pubitemid 46048464)
59. Lacasa D, Taleb S, Keophiphath M, et al. Macrophage-secreted factors impair human adipogenesis: involvement of proinfammatory state in preadipocytes. Endocrinology. 2007;148:868-877. (Pubitemid 46143186)
60. Sharma AM, Staels B. Review: peroxisome proliferator-activated receptor gamma and adipose tissue-understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab. 2007;92:386-395.
61. Shoelson SE, Lee J, Goldfne AB. Infammation and insulin resistance. J Clin Invest. 2006;116:1793-1801.
62. Lalor PF, Faint J, Aarbodem Y, et al. The role of cytokines and chemokines in the development of steatohepatitis. Semin Liver Dis. 2007;27:173-193. (Pubitemid 46871663)
63. Zeyda M, Stulnig TM. Adipose tissue macrophages. Immunol Lett. 2007;112:61-67. (Pubitemid 47379852)
64. Wigg AJ, Roberts-Tomson IC, Dymock RB, et al. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut. 2001;48:206-211. (Pubitemid 32141844)
65. Feldstein AE, Werneburg NW, Li Z, et al. Bax inhibition protects against free fatty acid-induced lysosomal permeabilization. Am J Physiol Gastrointest Liver Physiol. 2006;290:1339-1346.
66. Schwabe RF, Brenner DA. Mechanisms of liver injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol. 2006;290:583-589.
67. Yamauchi T, Nio Y, Maki T, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007;13: 332-339. (Pubitemid 46376688)
68. Wu X, Motoshima H, Mahadev K, et al. Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes. 2003;52:1355-1363. (Pubitemid 36666188)
69. Minokoshi Y, Kim YB, Peroni OD, et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002;415:339-343. (Pubitemid 34087557)
70. Saxena NK, Ikeda K, Rockey DC, et al. Leptin in hepatic fbrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. J Hepatol. 2002;35:761-771.
71. Leclercq IA, Farrell GC, Schriemer R, Robertson GR. Leptin is essential for the hepatic fbrogenic response to chronic liver injury. J Hepatol. 2002;37:206-213. (Pubitemid 34833082)
72. Muse ED, Lam TK, Scherer PE, Rossetti L. Hypothalamic resistin induces hepatic insulin resistance. J Clin Invest. 2007;117:1670-1678. (Pubitemid 46871351)
73. Tilg H, Moschen AR. Infammatory mechanisms in the regulation of insulin resistance. Mol Med. 2008;14:222-231. (Pubitemid 351481853)
74. Jager J, Gremeaux T, Cormont M, et al. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology. 2007;148:241-251. (Pubitemid 46021456)
75. Jin X, Zimmers TA, Perez EA, et al. Paradoxical Effects of short-and long-term interleukin-6 exposure on liver injury and repair. Hepatology. 2006;43:474-484.
76. Ardaillou R. Active fragments of angiotensin II: enzymatic pathways of synthesis and biological Effects. Curr Opin Nephrol Hypertens. 1997;6:28-34. (Pubitemid 27110154)
77. Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev. 2003;24:261-271. (Pubitemid 36733542)
78. Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87:1-9.
79. Schindler C, Bramlage P, Kirch W, Ferrario CM. Role of the vasodilator peptide angiotensin-(1-7) in cardiovascular drug therapy. Vasc Health Risk Manag. 2007;3:125-137. (Pubitemid 46860722)
80. Guo DF, Sun YL, Hamet P, Inagami T. The angiotensin II type 1 receptor and receptor-associated proteins. Cell Res. 2001;11: 165-180. (Pubitemid 33677246)
81. Kaschina E, Unger T. Angiotensin AT1/AT 2 receptors: regulation, signalling and function. Blood Press. 2003;12:70-88.
82. Santos RAS, Simoes e Silva AC, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci USA. 2003;100:8258-8263. (Pubitemid 36842532)
83. Velloso LA, Folli F. Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci USA. 1996;93: 12490-12495. (Pubitemid 26367171)
84. Zhai, P, Yamamoto M, Galeotti J, et al. Cardiac-specifc overexpression of AT1 receptor mutant lacking Gαq/Gαi coupling causes hypertrophy and bradycardia in transgenic mice. J Clin Invest. 2005;115:3045-3056. (Pubitemid 41567570)
85. Rajagopal K, Lefowitz RJ, Rockman HA. When 7 transmembrane receptors are not G protein-coupled receptors. J Clin Invest. 2005;115:2971-2974. (Pubitemid 41567561)
86. Kohout T, Lefowitz R. Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization. Mol Pharmacol. 2003;63:9-18. (Pubitemid 36043803)
87. Kenakin, T. Ligand-selective receptor conformations revisited: the promise and the problem. Trends Pharmacol Sci. 2003;24:346-354. (Pubitemid 37315526)
88. Nickenig G, Roling J, Bohm M, et al. Insulin induces upregulation of vascular AT-1 receptor gene expression by post-transcriptional mechanisms. Circulation. 1998;98:2453-2460. (Pubitemid 28549791)
89. Wei Y, Sowers JR, Nistala R, et al. Angiotensin II-induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells. J Biol Chem. 2006;281:35137-35146. (Pubitemid 46036553)
90. We i Y, Sowers JR, Clark SE, et al. Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-kappaB activation via NADPH oxidase. Am J Physiol Endocrinol Metab. 2008;294:345-351.
91. Motley ED, Eguchi K, Gardner C, et al. Insulin-induced Akt activation is inhibited by Angiotensin II in the vasculature through Protein Kinase C-α. Hypertension. 2003;41:775-780. (Pubitemid 36314590)
92. Izawa Y, Yoshizumi M, Fujita Y, et al. ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells. Exp Cell Res. 2005;308:291-299.
93. Engeli S, Negrel R, Sharma AM. Physiology and physiopathology of the adipose tissue renin-angiotensin system. Hypertension. 2000;35:1270-1277. (Pubitemid 30413663)
94. Matsushita K, Wu Y, Okamoto Y, et al. Local renin angiotensin expression regulates human mesenchymal stem cell diferentiation to adipocytes. Hypertension. 2006;48:1095-1102. (Pubitemid 44772713)
95. Saint-Marc P, Kozak LP, Ailhaud G, et al. Angiotensin II as a trophic factor of white adipose tissue: stimulation of adipose cell formation. Endocrinology. 2001;142:487-492. (Pubitemid 32183711)
96. Janke J, Engeli S, Gorzelniak K, et al. Mature adipocytes inhibit in vitro diferentiation of human preadipocytes via angiotensin type 1 receptors. Diabetes. 2002;51:1699-1707. (Pubitemid 34564280)
97. Mogi M, Iwai M, Horiuchi M. Emerging concept of adipogenesis aregulation by the rennin-angiotensin system. Hypertension. 2006;48:1020-1022. (Pubitemid 44772700)
98. Furuhashi M, Ura N, Takizawa H, et al. Blockade of the renin-angiotensin system decreases adipocyte size with improvement in insulin sensitivity. J Hypertens. 2004;22:1977-1982. (Pubitemid 39336681)
99. Santos SH, Fernandes LR, Mario EG, et al. Mas defciency in FVB/N mice produces marked changes in lipid and glycemic metabolism. Diabetes. 2008;57:340-347.
100. Borglum JD, Richelsen B, Darimont C, et al. Expression of the two isoforms of prostaglandin endoperoxide synthase (PGHS-1 and PGHS-2) during adipose cell diferentiation. Mol Cell Endocrinol. 1997;131:67-77. (Pubitemid 27343234)
101. Fain JN, Ballou LR, Bahouth SW. Obesity is induced in mice heterozygous for cyclooxygenase-2. Prostaglandins Other Lipid Mediat. 2001;65:199-209. (Pubitemid 32553882)
102. Jones BH, Standridge MK, Moustaid N. Angiotensin II increases lipogenesis in 3T3-L1 and human adipose cells. Endocrinology. 1997;138:1512-1519. (Pubitemid 27137101)
103. Kim S, Whelan J, Claycombe K, et al. Angiotensin II increases leptin secretion by 3T3-L1 and human adipocytes via a prostaglandin-independent mechanism. J Nutr. 2002;132:1135-1140. (Pubitemid 34606440)
104. Skurk T, van Harmelen V, Blum WF, Hauner H. Angiotensin II promotes leptin production in cultured human fat cells by an ERK1/2-dependent pathway. Obes Res. 2005;13:969-973.
105. Kim S, Soltani-Bejnood M, Quignard-Boulange A, et al. The adipose renin-angiotensin system modulates systemic markers of insulin sensitivity and activates the intrarenal renin-angiotensin system. J Biomed Biotechnol. 2006;2006:27012.
106. Fasshauer M, Klein J, Neumann S, et al. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2002;290:1084-1089. (Pubitemid 34687474)
107. Furuhashi M, Ura N, Higashiura K, et al. Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. Hypertension. 2003;42:76-81. (Pubitemid 36842239)
108. Xu SQ, Mahadev K, Wu X, et al. Adiponectin protects against angiotensin II or tumor necrosis factor alpha-induced endothelial cell monolayer hyperpermeability: role of cAMP/PKA signaling. Arterioscler Tromb Vasc Biol. 2008;28:899-905. (Pubitemid 351544105)
109. Nakamura A, Johns EJ, Imaizumi A, et al. Role of angiotensin II-induced cAMP in mesangial TNF-alpha production. Cytokine. 2002;19:47-51.
110. Bucher M, Ittner KP, Hobbhalm J, et al. Downregulation of angiotensin II-type 1 receptors during sepsis. Hypertension. 2001;38:177-182. (Pubitemid 34224740)
111. Cowling RT, Gurantz D, Peng J, et al. Transcription factor NF-kappa B is necessary for up-regulation of type 1 angiotensin II receptor mRNA in rat cardiac fbroblasts treated with tumor necrosis factor-alpha or interleukin-1 beta. J Biol Chem. 2003;277:5719-57124.
112. Skurk T, van Harmelen V, Hauner H. Angiotensin II stimulates the release of interleukin-6 and interleukin-8 from cultured human adipocytes by activation of NF-kappaB. Arterioscler Tromb Vasc Biol. 2004;24:1199-1203. (Pubitemid 38880008)
113. Schoonbroodt S, Piette J. Oxidative stress interference with the nuclear factor-kappa B activation pathways. Biochem Pharmacol. 2000;60:1075-1083.
114. Choudhary S, Lu M, Cui R, Brasier AR. Involvement of a novel Rac/RhoA guanosine triphosphatase-nuclear factor-kB inducing kinase signaling pathway mediating Angiotensin II-induced RelA transactivation. Mol Endocrinol. 2007;21:2203-2217. (Pubitemid 47347382)
115. Sironi L, Gelosa P, Guerrini U, et al. Anti-infammatory Effects of AT1 receptor blockade provide end-organ protection in stroke-prone rats independently from blood pressure fall. J Pharmacol Exp Ter. 2004;311:989-995. (Pubitemid 39612703)
116. Janssen SW, Hermus AR, Lange WP, et al. Progressive histopathological changes in pancreatic islets of Zucker diabetic fatty rats. Exp Clin Endocrinol Diabetes. 2001;109:273-282. (Pubitemid 32738112)
117. Lau T, Carlsson PO, Leung PS. Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets. Diabetologia. 2004;47:240-248. (Pubitemid 38315360)
118. Huang Z, Jansson L, Sjöholm A. Vasoactive drugs enhance pancreatic islet blood fow, augment insulin secretion and improve glucose tolerance in female rats. Clin Sci (Lond). 2007;112:69-76. (Pubitemid 46120087)
119. Carlsson PO, Berne C, Jansson L. Angiotensin II and the endocrine pancreas: Effects on islet blood fow and insulin secretion in rats. Diabetologia. 1998;41:127-133. (Pubitemid 28088387)
120. Dal Ponte DB, Fogt DL, Jacob S, Henriksen EJ. Interactions of captopril and verapamil on glucose tolerance and insulin action in an animal model of insulin resistance. Metabolism. 1998;47:982-987. (Pubitemid 28364618)
121. Tikellis C, Wookey PJ, Candido R, et al. Improved islet morphology afer blockade of the renin-angiotensin system in the ZDF rat. Diabetes. 2004;53:989-997. (Pubitemid 38436611)
122. Chu KY, Lau T, Carlsson PO, Leung PS. Angiotensin II type 1 receptor blockade improves beta-cell function and glucose tolerance in a mouse model of type 2 diabetes. Diabetes. 2006;55:367-374. (Pubitemid 43343265)
123. Ramracheya RD, Muller DS, Wu Y, et al. Direct regulation of insulin secretion by angiotensin II in human islets of Langerhans. Diabetologia. 2006;49:321-331. (Pubitemid 43185401)
124. Leung PS. The physiology of a local renin-angiotensin system in the pancreas. J Physiol. 2007;580:31-37. (Pubitemid 46470642)
125. Oliveira HR, Verlengia R, Carvalho CR, et al. Pancreatic β-cells express phagocyte-like NAD(P)H oxidase. Diabetes. 2003;52:1457-1463. (Pubitemid 36666201)
126. Lupi R, Del Guerra S, Bugliani M, et al. The direct Effects of the angiotensin-converting enzyme inhibitors, zofenoprilat and enalaprilat, on isolated human pancreatic islets. Eur J Endocrinol. 2006;154:355-361.
127. Habibi J, Whaley-Connell A, Hayden MR, et al. Renin inhibition attenuates insulin resistance, oxidative stress, and pancreatic remodeling in the transgenic Ren2 rat. Endocrinology. 2008; Jul 24. Epub ahead of print.
128. Sun Y, Zhang J, Zhang JQ, Ramires FJ. Local angiotensin II and transforming growth factor-beta1 in renal fbrosis of rats. Hypertension. 2000;35:1078-1084. (Pubitemid 30327261)
129. Chipitsyna G, Gong Q, Gray CF, et al. Induction of monocyte chemoattractant protein-1 expression by angiotensin II in the pancreatic islets and beta-cells. Endocrinology. 2007;148:2198-2208. (Pubitemid 46997051)
130. Hirose A, Ono M, Saibara T, et al. Angiotensin II type 1 receptor blocker inhibits fbrosis in rat nonalcoholic steatohepatitis. Hepatology. 2007;45: 1375-1381. (Pubitemid 46918321)
131. Warner FJ, Lubel JS, McCaughan GW, et al. Liver fbrosis: a balance of ACEs? Clin Sci (Lond). 2007;113:109-118.
132. Nabeshima Y, Tazuma S, Kanno K, et al. Anti-fbrogenic function of angiotensin II type 2 receptor in CCl4-induced liver fbrosis. Biochem Biophys Res Commun. 2006;346:658-664.
133. Bataller R, Gäbele E, Schoonhoven R, et al. Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and proinfammatory events in liver. Am J Physiol Gastrointest Liver Physiol. 2003;285:642-651.
134. Toblli JE, Muñoz MC, Cao G, et al. ACE inhibition and AT1 receptor blockade prevent fatty liver and fbrosis in obese Zucker rats. Obesity (Silver Spring). 2008;16:770-776. (Pubitemid 351465631)
135. Takeshita Y, Takamura T, Takazakura A, et al. Cross talk of tumor necrosis factor-alpha and the renin-angiotensin system in tumor necrosis factor-alpha-induced plasminogen activator inhibitor-1 production from hepatocytes. Eur J Pharmacol. 2008;579:426-432.
136. Ruiz-Ortega M, Lorenzo O, Suzuki Y, et al. Proinfammatory actions of angiotensins. Curr Opin Nephrol Hypertens. 2001;10:321-329.
137. Jamaluddin M, Meng T, Sun J, et al. Angiotensin II induces nuclear factor (NF)-kappaB1 isoforms to bind the angiotensinogen gene acute-phase response element: a stimulus-specifc pathway for NF-kappaB activation. Mol Endocrinol. 2000;14:99-113. (Pubitemid 32260330)
138. Ramadori G, Saile B. Portal tract fbrogenesis in the liver. Lab Invest. 2004;84:153-159.
139. Gabele E, Brenner DA, Rippe RA. Liver fbrosis: signals leading to the amplifcation of the fbrogenic hepatic stellate cell. Front Biosci. 2003;8:69-77.
140. Bataller R, Sancho-Bru P, Ginès P, et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003;125:117-125. (Pubitemid 36799113)
141. Bataller R, Brenner DA. Liver fbrosis. J Clin Invest. 2005;115:209-218.
142. Wynn TA. Cellular and molecular mechanisms of fbrosis. J Pathol. 2008;214:199-210.
143. Gorelik L, Flavell RA. Transforming growth factor in T-cell biology. Nat Rev Immunol. 2002;2:46-53. (Pubitemid 37328775)
144. Roberts AB, Russo A, Felici A, Flanders KC. Smad3: a key player in pathogenetic mechanisms dependent on TGF. Ann NY Acad Sci. 2003;995:1-10. (Pubitemid 36706609)
145. Schnabl B, Kweon YO, Frederick JP, et al. The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology. 2001;34:89-100. (Pubitemid 32591487)
146. Baik SK, Jo HS, Suk K T, et al. Inhibitory Effect of angiotensin 2 receptor antagonist on the contraction and growth of hepatic stellate cells. Korean J Gastroenterol. 2003;42:134-141.
147. Liu J, Gong H, Zhang Z, Wang Y. Effect of angiotensin II and angiotensin II type I receptor antagonist on the proliferation, contraction and collagen synthesis in rat hepatic stellate cells. Chinese Med J. 2008;121:161-165. (Pubitemid 351247891)
148. Yoshiji H, Kuriyama S, Fukui H. Blockade of renin-angiotensin system in antifbrotic therapy. J Gastroenterol Hepatol. 2007;22(suppl. 1):93-95.
149. Gillespie EL, White CM, Kardas M, et al. The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. Diabetes Care. 2005;28:2261-2266. (Pubitemid 41242483)
150. Abuissa H, Jones PG, Marso SP, O'Keefe JH Jr. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes. A meta-analysis of randomized clinical trials. J Am Coll Cardiol. 2005;46:821-826. (Pubitemid 41224805)
151. Israili ZH. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens. 2000;14(suppl. 1):73-86.
152. Oparil S. Newly emerging pharmacologic diferences in angiotensin II receptor blockers. Am J Hypertens. 2000;13:18-24.
153. Unger T. Signifcance of angiotensin type 1 receptor blockade: why are angiotensin II receptor blockers diferent? Am J Cardiol. 1999;84:9-15.
154. Clemenz M, Frost N, Schupp MN, et al. Liver-specifc peroxisome proliferator-activated receptor alpha target gene regulation by the angiotensin type 1 receptor blocker telmisartan. Diabetes. 2008;57:1405-1413.
155. Grange RL, Ziogas J, North AJ, et al. Selenosartans: novel selenophene analogues of milfasartan and eprosartan. Bioorg Med Chem Lett. 2008;18:1241-1244. (Pubitemid 351179368)
156. Georgescu EF, Georgescu M. Terapeutic options in non-alcoholic steatohepatitis (NASH). Are all agents alike? Results of a preliminary study. J Gastrointestin Liver Dis. 2007;16:39-46. (Pubitemid 46548588)
157. Yokohama S, Tokusashi Y, Nakamura K, et al. Inhibitory Effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis. World J Gastroenterol. 2006;12:322-326. (Pubitemid 43336936)
158. Yokohama S, Yoneda M, Haneda M, et al. Terapeutic efcacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology. 2004;40:1222-1225. (Pubitemid 39425579)
159. Zhang YJ, Yang XS, Wu PS, et al. Effects of angiotensin II and losartan on the growth and proliferation of hepatic stellate cells. Di Yi Jun Yi Da Xue Xue Bao. 2003;23:219-221.
160. Wei YH, Jun L, Qiang CJ. Effect of losartan, an angiotensin II antagonist, on hepatic fbrosis induced by CCl4 in rats. Dig Dis Sci. 2004;49:1589-1594. (Pubitemid 39335540)
161. Wei HS, Lu HM, Li DG, et al. The regulatory role of AT 1 receptor on activated HSCs in hepatic fbrogenesis:Effects of RAS inhibitors on hepatic fbrosis induced by CCl(4). World J Gastroenterol. 2000;6:824-828. (Pubitemid 32015797)
162. Wei HS, Li DG, Lu HM, et al. Effects of AT1 receptor antagonist, losartan, on rat hepatic fbrosis induced by CCl(4). World J Gastroenterol. 2000;6:540-545. (Pubitemid 30665265)
163. Ibañez P, Solis N, Pizarro M, et al. Effect of losartan on early liver fbrosis development in a rat model of nonalcoholic steatohepatitis. J Gastroenterol Hepatol. 2007;22:846-851. (Pubitemid 46911021)
164. Kobayashi N, Ohno T, Yoshida K, et al. Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. Am J Hypertens. 2008;21:576-581. (Pubitemid 351589680)
165. Georgescu EF, Ionescu R, Georgescu M, et al. Are angiotensin-receptor blockers candidates for frst choice treatment in non-alcoholic steatohepatitis associated to mild-to moderate hypertension? J Hepatol. 2008;48(suppl. 2):346-347.
166. Fujita K, Yoneda M, Wada K, et al. Telmisartan, an angiotensin II type 1 receptor blocker, controls progress of nonalcoholic steatohepatitis in rats. Dig Dis Sci. 2007;52:3455-3464. (Pubitemid 350077187)
167. Jin H, Yamamoto N, Uchida K, et al. Telmisartan prevents hepatic fbrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-defcient L-amino acid-defned diet. Biochem Biophys Res Commun. 2007;364:801-807. (Pubitemid 350103697)
168. Sugimoto K, Qi NR, Kazdová L, et al. Telmisartan but not valsartan increases caloric expenditure and protects against weight gain and hepatic steatosis. Hypertension. 2006;47:822-823.
169. Yoshida T, Yamagishi S, Matsui T, et al. Telmisartan, an angiotensin II type 1 receptor blocker, inhibits advanced glycation end-product (AGE)-elicited hepatic insulin resistance via peroxisome proliferator-activated receptor-gamma activation. J Int Med Res. 2008;36:237-243. (Pubitemid 351516604)
170. Yamada S, Ano N, Toda K. Telmisartan but not candesartan afects adiponectin expression in vivo and in vitro. Hypertens Res. 2008;31:601-606. (Pubitemid 351772849)
171. Derosa G, Ragonesi PD, Mugellini A, et al. Effects of telmisartan compared with eprosartan on blood pressure control glucose metabolism and lipid profle in hypertensive, type 2 diabetic patients: a randomized, double-blind, placebo-controlled 12-month study. Hypertens Res. 2004;27:457-464. (Pubitemid 39157547)
172. Shimabukuro M, Tanaka H, Shimabukuro T. Effects of telmisartan on fat distribution in individuals with the metabolic syndrome. J Hypertens. 2007;25:841-848. (Pubitemid 46398879)
173. Benndorf RA, Rudolph T, Appel D, et al. Telmisartan improves insulin sensitivity in nondiabetic patients with essential hypertension. Metabolism. 2006;55:1159-1164. (Pubitemid 44219053)
174. Araki K, Masaki T, Katsuragi I, et al. Telmisartan prevents obesity and increases the expression of uncoupling protein 1 in diet-induced obese mice. Hypertension. 2006;48:51-57. (Pubitemid 44297524)
175. Cianchetti S, Del Fiorentino A, Colognato R, et al. Anti-infammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells. Atherosclerosis. 2008;198:22-28. (Pubitemid 351406364)
176. Yoshida T, Yamagishi S, Nakamura K, et al. Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation. Diabetologia. 2006;49:3094-3099. (Pubitemid 44730314)
177. Walcher D, Hess K, Heinz P, et al. Telmisartan inhibits CD4-positive lymphocyte migration independent of the angiotensin type 1 receptor via peroxisome proliferator-activated receptor-gamma. Hypertension. 2008;51:259-266. (Pubitemid 351159937)
178. Ran J, Hirano T, Adachi M. Angiotensin II infusion increases hepatic triglyceride production via its type 2 receptor in rats. J Hypertens. 2005;23:1525-1530. (Pubitemid 41104824)
179. Ran J, Hirano T, Adachi M. Angiotensin II type 1 receptor blocker ameliorates overproduction and accumulation of triglyceride in the liver of Zucker fatty rats. Am J Physiol Endocrinol Metab. 2004;287:227-232.
180. Kurikawa N, Suga M, Kuroda S, et al. An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fbrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells. Br J Pharmacol. 2003;139:1085-1094. (Pubitemid 36920670)
181. Debernardi-Venon W, Martini S, Biasi F, et al. AT 1 receptor antagonist candesartan in selected cirrhotic patients: Effect on portal pressure and liver fbrosis markers. J Hepatol. 2007;46:1026-1033. (Pubitemid 46669730)
182. Yu F, Takahashi T, Moriya J, et al. Angiotensin-II receptor antagonist alleviates non-alcoholic fatty liver in KKAy obese mice with type 2 diabetes. J Int Med Res. 2006;34:297-302. (Pubitemid 44057273)
183. Yoshiji H, Kuriyama S, Yoshii J. Angiotensin-II type 1 receptor interaction is a major regulator for liver fbrosis development in rats. Hepatology. 2001;34:745-750. (Pubitemid 32927999)
184. Ueki M, Koda M, Yamamoto S, et al. Preventive and therapeutic Effects of angiotensin II type 1 receptor blocker on hepatic fbrosis induced by bile duct ligation in rats. J Gastroenterol. 2006;41:996-1004. (Pubitemid 44741413)
185. Töx U, Scheller I, Kociok N, et al. Expression of angiotensin II receptor type 1 is reduced in advanced rat liver fbrosis. Dig Dis Sci. 2007;52:1995-2005. (Pubitemid 47024643)
186. Tuncer I, Ozbek H, Ugras S, et al. Anti-fbrogenic Effects of captopril and candesartan cilexetil on the hepatic fbrosis development in rat. The Effect of AT1-R blocker on the hepatic fbrosis. Exp Toxicol Pa t h ol. 2003;55:159-166. (Pubitemid 37309765)
187. Clasen R, Schupp M, Foryst-Ludwig A, et al. PPAR gamma activating angiotensin type 1 receptor blockers induce adiponectin. Hypertension. 2005;46:137-143. (Pubitemid 40946504)
188. Erbe DV, Gartrell K, Zhang YL, et al. Molecular activation of PPARgamma by angiotensin II type 1-receptor antagonists. Vascul Pharmacol. 2006;45:154-162. (Pubitemid 44716729)
189. Nie L, Imamura M, Itoh H, Ueno H. Pitavastatin enhances the anti-fbrogenesis Effects of candesartan, an angiotensin II receptor blocker, on CCl4-induced liver fbrosis in rats. J UOEH. 2004;26:165-177. (Pubitemid 38855686)
190. Wei Y, Clark SE, Morris EM, et al. Angiotensin II-induced non-alcoholic fatty liver disease is mediated by oxidative stress in transgenic TG(mRen2)27(Ren2) rats. J Hepatol. 2008;49:417-428.
191. Ilanne-Parikka P, Eriksson JG, Lindström J, et al. Prevalence of the metabolic syndrome and its components: fndings from a Finnish general population sample and the Diabetes Prevention Study cohort. Diabetes Care. 2004;27:2135-2140. (Pubitemid 39167175)
192. Mancia G, Bombelli M, Corrao G, et al. Metabolic syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study: daily life blood pressure, cardiac damage, and prognosis. Hypertension. 2007;49:40-47. (Pubitemid 46360339)
193. Govindarajan G, Whaley-Connell A, Mugo M, et al. The cardiometabolic syndrome as a cardiovascular risk factor. Am J Med Sci. 2005;330:311-318. (Pubitemid 41831902)