Hepatic endothelial dysfunction and abnormal angiogenesis: New targets in the treatment of portal hypertension

Journal of Hepatology

Volumn 53, Issue 3, 2010, Pages 558-567

  Bosch, Jaume ^a   Abraldes, Juan G ^a   Fernández, Mercedes ^a   García Pagán, Juan Carlos ^a  

^a INSTITUTO DE SALUD CARLOS III   (Spain)

Author keywords

Angiogenesis; Hepatic endothelial dysfunction; Portal hypertension

Indexed keywords

ANGIOGENESIS INHIBITOR; ASCORBIC ACID; ATORVASTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; NITRIC OXIDE; PROPRANOLOL; ROSUVASTATIN; SIMVASTATIN; SUPEROXIDE DISMUTASE; TETRAHYDROBIOPTERIN;

ADULT; ANGIOGENESIS; BLOOD VESSEL TONE; CHRONIC LIVER DISEASE; ENDOTHELIAL DYSFUNCTION; FIBRIN FORMATION; HUMAN; INFLAMMATION; LIVER FIBROSIS; NONHUMAN; PATHOPHYSIOLOGY; PORTAL HYPERTENSION; PORTAL VEIN THROMBOSIS; PRIORITY JOURNAL; REVIEW; SPLANCHNIC BLOOD FLOW; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; VASCULAR RESISTANCE; VASODILATATION; VENOUS THROMBOEMBOLISM;

ANTIOXIDANTS; BIOPTERIN; ENDOTHELIUM, VASCULAR; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERTENSION, PORTAL; LIVER; NEOVASCULARIZATION, PATHOLOGIC; NITRIC OXIDE; PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES; PROSTAGLANDINS; SIGNAL TRANSDUCTION; SPLANCHNIC CIRCULATION; VASCULAR RESISTANCE;

EID: 77955853856     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jhep.2010.03.021     Document Type: Review

References (87)

1. J. Bosch, A. Berzigotti, J.C. Garcia-Pagan, and J.G. Abraldes The management of portal hypertension: rational basis, available treatments and future options J Hepatol 48 2008 S68 S92
2. M. Hernandez-Guerra, J.C. Garcia-Pagan, and J. Bosch Increased hepatic resistance: a new target in the pharmacologic therapy of portal hypertension J Clin Gastroenterol 39 2005 S131 S137
3. J. Vorobioff, J.E. Bredfeldt, and R.J. Groszmann Increased blood flow through the portal system in cirrhotic rats Gastroenterology 87 1984 1120 1123
4. M.P. Pizcueta, J.C. Garcia-Pagan, M. Fernandez, R. Casamitjana, J. Bosch, and J. Rodes Glucagon hinders the effects of somatostatin on portal hypertension. A study in rats with partial portal vein ligation Gastroenterology 101 1991 1710 1715
5. M.P. Pizcueta, R. Casamitjana, J. Bosch, and J. Rodes Decreased systemic vascular sensitivity to norepinephrine in portal hypertensive rats: role of hyperglucagonism Am J Physiol 258 1990 G191 G195
6. M. Fernandez, D. Semela, J. Bruix, I. Colle, M. Pinzani, and J. Bosch Angiogenesis in liver disease J Hepatol 50 2009 604 620
7. K. Kaneda, M. Sogawa, A. Matsumara, A. Cho, and N. Kawada Endothelin-1 induced vasoconstriction causes a significant increase in portal pressure of rat liver: localized constrictive effect on the the distal segment of preterminal portal venules as revealed by light and electron microscopy and serial reconstruction Hepatology 27 1998 735 747
8. J.X. Zhang, W. Pegoli Jr, and M.G. Clemens Endothelin-1 induces direct constriction of hepatic sinusoids Am J Physiol (Gastrointest Liver Physiol) 29 1994 G264 G632
9. N. Kawada, T.A. Tran-Thi, H. Klein, and K. Decker The contraction of hepatic stellate (Ito) cells stimulated with vasoactive substances. Possible involvement of endothelin 1 and nitric oxide in the regulation of the sinusoidal tonus Eur J Biochem 213 1993 815 823
10. D.G. Harrison Cellular and molecular mechanisms of endothelial cell dysfunction J Clin Invest 100 1997 2153 2157
11. D.G. Harrison Endothelial function and oxidant stress Clin Cardiol 20 1997 II-7
12. T.K. Gupta, M. Toruner, M.K. Chung, and R.J. Groszmann Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats Hepatology 28 1998 926 931
13. L. Bellis, A. Berzigotti, J.G. Abraldes, E. Moitinho, J.C. Garcia-Pagan, and J. Bosch Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis Hepatology 37 2003 378 384
14. M. Graupera, J.C. Garcia-Pagan, M. Pares, J.G. Abraldes, J. Rosello, and J. Bosch Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers J Hepatol 39 2003 515 521
15. T. Miyamoto, N. Ogino, S. Yamamoto, and O. Hayaishi Purification of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes J Biol Chem 251 1976 2629 2636
16. W.L. Smith Prostanoid biosynthesis and mechanisms of action Am J Physiol 263 1992 F181 F191
17. W.L. Smith, R.M. Garavito, and D.L. DeWitt Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2 J Biol Chem 271 1996 33157 33160
18. W.L. Smith, and R. Langenbach Why there are two cyclooxygenase isozymes J Clin Invest 107 2001 1491 1495
19. M. Graupera, J.C. Garcia-Pagan, J.G. Abraldes, C. Peralta, M. Bragulat, and H. Corominola Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers Hepatology 37 2003 172 181
20. M.A. Potenza, O.A. Botrugno, M.A. De Salvia, G. Lerro, C. Nacci, and F.L. Marasciulo Endothelial COX-1 and -2 differentially affect reactivity of MVB in portal hypertensive rats Am J Physiol Gastrointest Liver Physiol 283 2002 G587 G594
21. J. Gracia-Sancho, B. Lavina, A. Rodriguez-Vilarrupla, H. Garcia-Caldero, J. Bosch, and J.C. Garcia-Pagan Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers J Hepatol 47 2007 220 227
22. C.J. Steib, A.L. Gerbes, M. Bystron, W.M. Op den, J. Hartl, and F. Roggel Kupffer cell activation in normal and fibrotic livers increases portal pressure via thromboxane A(2) J Hepatol 47 2007 228 238
23. S. Moncada, and A. Higgs The l-arginine-nitric oxide pathway N Engl J Med 329 1993 2002 2012
24. M.K. Mittal, T.K. Gupta, F.Y. Lee, C.C. Sieber, and R.J. Groszmann Nitric oxide modulates hepatic vascular tone in normal rat liver Am J Physiol 267 1994 G416 G422
25. D.R. Miller, J.M. Collier, and R.E. Billings Protein tyrosine kinase activity regulates nitric oxide synthase induction in rat hepatocytes Am J Physiol 272 1997 G207 G214
26. V. Shah, M. Toruner, F. Haddad, G. Cadelina, A. Papapetropoulos, and K. Choo Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat Gastroenterology 117 1999 1222 1228
27. S. Fiorucci, E. Antonelli, V. Brancaleone, L. Sanpaolo, S. Orlandi, and E. Distrutti NCX-1000, a nitric oxide-releasing derivative of ursodeoxycholic acid, ameliorates portal hypertension and lowers norepinephrine-induced intrahepatic resistance in the isolated and perfused rat liver J Hepatol 39 2003 932 939
28. A. Berzigotti, P. Bellot, A. de Gotardi, J.C. Garcia-Pagan, C. Gagnon, and J. Spénard NCX-1000, a Nitric oxide-releasing derivative of UDCA, does not decrease portal pressure in patients with cirrhosis: results of a randomized, double-blind, dose-escalating study Am J Gastroenterol 105 2010 1094 1101
29. M. Van de Casteele, A. Omasta, S. Janssens, T. Roskams, V. Desmet, and F. Nevens In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats Gut 51 2002 440 445
30. V. Shah, A.F. Chen, S. Cao, H. Hendrickson, D. Weiler, and L. Smith Gene transfer of recombinant endothelial nitric oxide synthase to liver in vivo and in vitro Am J Physiol Gastrointest Liver Physiol 279 2000 G1023 G1030
31. Q. Yu, R. Shao, H.S. Qian, S.E. George, and D.C. Rockey Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension J Clin Invest 105 2000 741 748
32. M. Morales-Ruiz, P. Cejudo-Martin, G. Fernandez-Varo, S. Tugues, J. Ros, and P. Angeli Transduction of the liver with activated Akt normalizes portal pressure in cirrhotic rats Gastroenterology 125 2003 522 531
33. J.G. Abraldes, A. Rodriguez-Vilarrupla, M. Graupera, C. Zafra, H. Garcia-Caldero, and J.C. Garcia-Pagan Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats J Hepatol 46 2007 1040 1046
34. C. Zafra, J.G. Abraldes, J. Turnes, A. Berzigotti, M. Fernandez, and J.C. Garca-Pagan Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis Gastroenterology 126 2004 749 755
35. B. Lavina, J. Gracia-Sancho, A. Rodriguez-Vilarrupla, Y. Chu, D.D. Heistad, and J. Bosch Superoxide dismutase gene transfer reduces portal pressure in CCl4 cirrhotic rats with portal hypertension Gut 58 2009 118 125
36. M. Hernandez-Guerra, J.C. Garcia-Pagan, J. Turnes, P. Bellot, R. Deulofeu, and J.G. Abraldes Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension Hepatology 43 2006 485 491
37. V. Matei, A. Rodriguez-Vilarrupla, R. Deulofeu, D. Colomer, M. Fernandez, and J. Bosch The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis Hepatology 44 2006 44 52
38. J. Gracia-Sancho, B. Lavina, A. Rodriguez-Vilarrupla, H. Garcia-Caldero, M. Fernandez, and J. Bosch Increased oxidative stress in cirrhotic rat livers: a potential mechanism contributing to reduced nitric oxide bioavailability Hepatology 47 2008 1248 1256
39. J. Bosch, J.G. Abraldes, and R.J. Groszmann Current management of portal hypertension J Hepatol 38 2003 S54 S68
40. P. Failli, R.M. De franco, A. Caligiuri, A. Gentilini, R.G. Romanelli, and F. Marra Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells Gastroenterology 119 2000 479 492
41. G. Dangas, D.A. Smith, A.H. Unger, J.H. Shao, P. Meraj, and C. Fier Pravastatin: an antithrombotic effect independent of the cholesterol-lowering effect Thromb Haemost 83 2000 688 692
42. D.J. Lefer Statins as potent antiinflammatory drugs Circulation 106 2002 2041 2042
43. Y. Kureishi, Z. Luo, I. Shiojima, A. Bialik, D. Fulton, and D.J. Lefer The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals Nat Med 6 2000 1004 1010
44. K. Bates, C.E. Ruggeroli, S. Goldman, and M.A. Gaballa Simvastatin restores endothelial NO-mediated vasorelaxation in large arteries after myocardial infarction Am J Physiol Heart Circ Physiol 283 2002 H768 H775
45. U. Laufs, K. Gertz, U. Dirnagl, M. Bohm, G. Nickenig, and M. Endres Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice Brain Res 942 2002 23 30
46. L. Kalinowski, L.W. Dobrucki, V. Brovkovych, and T. Malinski Increased nitric oxide bioavailability in endothelial cells contributes to the pleiotropic effect of cerivastatin Circulation 105 2002 933 938
47. D. Fulton, J.P. Gratton, T.J. McCabe, J. Fontana, Y. Fujio, and K. Walsh Regulation of endothelium-derived nitric oxide production by the protein kinase Akt Nature 399 1999 597 601
48. U. Laufs, V. La Fata, J. Plutzky, and J.K. Liao Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors Circulation 97 1998 1129 1135
49. J. Trebicka, M. Hennenberg, W. Laleman, N. Shelest, E. Biecker, and M. Schepke Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase Hepatology 46 2007 242 253
50. J.G. Abraldes, A. Albillos, R. Banares, J. Turnes, R. Gonzalez, and J.C. Garcia-Pagan Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial Gastroenterology 136 2009 1651 1658
51. R. Mastai, J. Bosch, M. Navasa, D. Kravetz, J. Bruix, and C. Viola Effects of alpha-adrenergic stimulation and beta-adrenergic blockade on azygos blood flow and splanchnic haemodynamics in patients with cirrhosis J Hepatol 4 1987 71 79
52. U. Ritzel, U. Leonhardt, M. Nather, G. Schafer, V.W. Armstrong, and G. Ramadori Simvastatin in primary biliary cirrhosis: effects on serum lipids and distinct disease markers J Hepatol 36 2002 454 458
53. N. Chalasani Statins and hepatotoxicity: focus on patients with fatty liver Hepatology 41 2005 690 695
54. R. Vuppalanchi, E. Teal, and N. Chalasani Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes Am J Med Sci 329 2005 62 65
55. S. Khorashadi, N.K. Hasson, and R.C. Cheung Incidence of statin hepatotoxicity in patients with hepatitis C Clin Gastroenterol Hepatol 4 2006 902 907
56. T. Stojakovic, C. Putz-Bankuti, G. Fauler, H. Scharnagl, M. Wagner, and V. Stadlbauer Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid Hepatology 46 2007 776 784
57. J.D. Browning Statins and hepatic steatosis: perspectives from the Dallas Heart Study Hepatology 44 2006 466 471
58. J.H. Lewis, M.E. Mortensen, S. Zweig, M.J. Fusco, J.R. Medoff, and R. Belder Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial Hepatology 46 2007 1453 1463
59. J.G. O'Leary, J.L. Chan, C.M. McMahon, and R.T. Chung Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: a pilot clinical trial Hepatology 45 2007 895 898
60. C.K. Argo, P. Loria, S.H. Caldwell, and A. Lonardo Statins in liver disease: a molehill, an iceberg, or neither? Hepatology 48 2008 662 669
61. M. Moreno, L.N. Ramalho, P. Sancho-Bru, M. Ruiz-Ortega, F. Ramalho, and J.G. Abraldes Atorvastatin attenuates angiotensin II-induced inflammatory actions in the liver Am J Physiol Gastrointest Liver Physiol 296 2009 G147 G156
62. R.J. Glynn, E. Danielson, and F. Fonseca A randomized trial of rosuvastatin in the prevention of venous thromboembolism N Engl J Med 360 2009 1851 1861
63. C. Francoz, J. Belghiti, V. Vilgrain, D. Sommacale, V. Paradis, and B. Condat Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation Gut 54 2005 691 697
64. M.A. Zocco, S.E. Di, C.R. De, M. Novi, M.E. Ainora, and F. Ponziani Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development J Hepatol 51 2009 682 689
65. V. Matei, A. Rodriguez-Vilarrupla, R. Deulofeu, H. Garcia-Caldero, M. Fernandez, and J. Bosch Three-day tetrahydrobiopterin therapy increases in vivo hepatic NOS activity and reduces portal pressure in CCl4 cirrhotic rats J Hepatol 49 2008 192 197
66. R.E. Huie, and S. Padmaja The reaction of no with superoxide Free Radic Res Commun 18 1993 195 199
67. H. Cai, and D.G. Harrison Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress Circ Res 87 2000 840 844
68. H. Lum, and K.A. Roebuck Oxidant stress and endothelial cell dysfunction Am J Physiol Cell Physiol 280 2001 C719 C741
69. D. Jay, H. Hitomi, and K.K. Griendling Oxidative stress and diabetic cardiovascular complications Free Radic Biol Med 40 2006 183 192
70. D.D. Heistad Oxidative stress and vascular disease: 2005 Duff lecture Arterioscler Thromb Vasc Biol 26 2006 689 695
71. M.P. Pizcueta, A.M. de Lacy, D. Kravetz, J. Bosch, and J. Rodes Propranolol decreases portal pressure without changing portocollateral resistance in cirrhotic rats Hepatology 10 1989 953 957
72. P. Carmeliet Mechanisms of angiogenesis and arteriogenesis Nat Med 6 2000 389 395
73. J. Folkman, and P.A. D'Amore Blood vessel formation: what is its molecular basis? Cell 87 1996 1153 1155
74. M. Fernandez, F. Vizzutti, J.C. Garcia-Pagan, J. Rodes, and J. Bosch Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice Gastroenterology 126 2004 886 894
75. M. Mejias, E. Garcia-Pras, C. Tiani, R. Miquel, J. Bosch, and M. Fernandez Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats Hepatology 49 2009 1245 1256
76. J. Medina, A.G. Arroyo, F. Sanchez-Madrid, and R. Moreno-Otero Angiogenesis in chronic inflammatory liver disease Hepatology 39 2004 1185 1195
77. R. Bataller, and D.A. Brenner Liver fibrosis J Clin Invest 115 2005 209 218
78. M. Fernandez, M. Mejias, B. Angermayr, J.C. Garcia-Pagan, J. Rodes, and J. Bosch Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats J Hepatol 43 2005 98 103
79. M. Fernandez, M. Mejias, E. Garcia-Pras, R. Mendez, J.C. Garcia-Pagan, and J. Bosch Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats Hepatology 46 2007 1208 1217
80. S. Tugues, G. Fernandez-Varo, J. Munoz-Luque, J. Ros, V. Arroyo, and J. Rodes Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats Hepatology 46 2007 1919 1926
81. B. Escudier, T. Eisen, W.M. Stadler, C. Szczylik, S. Oudard, and M. Siebels Sorafenib in advanced clear-cell renal-cell carcinoma N Engl J Med 356 2007 125 134
82. J.M. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane, and J.F. Blanc Sorafenib in advanced hepatocellular carcinoma N Engl J Med 359 2008 378 390
83. P. Carmeliet Angiogenesis in health and disease Nat Med 9 2003 653 660
84. V.H. Shah, and J. Bruix Antiangiogenic therapy: not just for cancer anymore? Hepatology 49 2009 1066 1068
85. S.C. Van, A. Geerts, E. Vanheule, V.H. Van, V.F. De, and K. Olievier Role of placental growth factor in mesenteric neoangiogenesis in a mouse model of portal hypertension Gastroenterology 2009
86. O. Feron, C. Dessy, J.P. Desager, and J.L. Balligand Hydroxy- methylglutaryl-coenzyme A reductase inhibition promotes endothelial nitric oxide synthase activation through a decrease in caveolin abundance Circulation 103 2001 113 118
87. Y. Hattori, N. Nakanishi, K. Akimoto, M. Yoshida, and K. Kasai HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells Arterioscler Thromb Vasc Biol 23 2003 176 182