Springer Seminars in Immunopathology

, Volume 20, Issue 1–2, pp 73–94 | Cite as

Angiogenesis in rheumatoid arthritis: implications for future therapeutic strategies

  • Ewa M. Paleolog
  • Roy A. Fava


Rheumatoid Arthritis Arthritis Internal Medicine Therapeutic Strategy Future Therapeutic Strategy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Badolato R, Ponzi AN, Millesimo M, Notarangelo LD, Musso T (1997) Interleukin-15 (IL-15) induces IL-8 and monocyte chemotactic protein 1 production in human monocytes. Blood 90: 2804Google Scholar
  2. 2.
    Baggiolini M, Dewald B, Moser B (1997) Human chemokines: an update. Annu Rev Immunol 15: 675Google Scholar
  3. 3.
    Benjamin LE, Keshet E (1997) Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc Natl Acad Sci USA 94: 8761Google Scholar
  4. 4.
    Blake DR, Merry P, Unsworth J, Kidd BL, Outhwaite JM, Ballard R, Morris CJ, Gray L, Lunec J (1989) Hypoxic-reperfusion injury in the inflamed human joint. Lancet I: 289Google Scholar
  5. 5.
    Bornstein P, Sage EH (1994) Thrombospondins. Methods Enzymol 245: 62Google Scholar
  6. 6.
    Brennan FM, Chantry D, Jackson A, Maini R, Feldmann M (1989) Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet II: 244Google Scholar
  7. 7.
    Brennan FM, Zachariae CO, Chantry D, Larsen CG, Turner M, Maim RN, Matsushima K, Feldmann M (1990) Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. Eur J Immunol 20: 2141Google Scholar
  8. 8.
    Brock TA, Dvorak HF, Senger DR (1991) Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Am J Pathol 138: 213Google Scholar
  9. 9.
    Brooks PC (1996) Role of integrins in angiogenesis. Eur J Cancer 32A: 2423Google Scholar
  10. 10.
    Brown LF, Detmar M, Claffey K, Nagy JA, Feng D, Dvorak AM, Dvorak HF (1997) Vascular permeability factor/vascular endothelial growth factor: a multifunctional angiogenic cytokine. EXS 79: 233Google Scholar
  11. 11.
    Brown RA, Weiss JB, Tomlinson IW, Phillips P, Kumar S (1980) Angiogenic factor from synovial fluid resembling that from tumours. Lancet I: 682Google Scholar
  12. 12.
    Burgess WH, Maciag T (1989) The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem 58:575Google Scholar
  13. 13.
    Cao Y, Chen C, Weatherbee JA, Tsang M, Folkman J (1995) gro-beta, a -C-X-C- chemokine, is an angiogenesis inhibitor that suppresses the growth of Lewis lung carcinoma in mice. J Exp Med 182:2069Google Scholar
  14. 14.
    Chu CQ, Field M, Allard S, Abney E, Feldmann M, Maini RN (1992) Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair. Br J Rheumatol 31: 653Google Scholar
  15. 15.
    Claesson-Welsh L (1994) Platelet-derived growth factor receptor signals. J Biol Chem 269: 32023Google Scholar
  16. 16.
    Cox DA, Maurer T (1997) Transforming growth factor-beta. Clin Immunol Immunopathol 83: 25Google Scholar
  17. 17.
    Dawson DW, Pearce SF, Zhong R, Silverstein RL, Frazier WA, Bouck NP (1997) CD36 mediates the in vitro inhibitory effects of thrombospondin-1 on endothelial cells. J Cell Biol 138: 707Google Scholar
  18. 18.
    DiPietro LA, Polverini PJ (1993) Angiogenic macrophages produce the angiogenic inhibitor thrombospondin 1. Am J Pathol 143:678Google Scholar
  19. 19.
    DiPletro LA, Nebgen DR, Polverini PJ (1994) Downregulation of endothelial cell thrombospondin I enhances in vitro angiogenesis. J Vase Res 31:178Google Scholar
  20. 20.
    Fava RA, Olsen NJ, Postlethwaite AE, Broadley KN, Davidson JM, Nanney LB, Lucas C, Townes AS (1991) Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia. J Exp Med 173: 1121Google Scholar
  21. 21.
    Fava RA, Olsen NJ, Spencer-Green G, Yeo KT, Yeo TK, Berse B, Jackman RW, Senger DR, Dvorak HF, Brown LF (1994) Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med 180: 341Google Scholar
  22. 22.
    Fava RA, Hunt JA, Yeo KT, Brown F, Berse B (1995) Induction of vascular permeability factor (vascular endothelial growth factor) by TGFP in synovial fibroblasts. Arthritis Rheum 38: S343Google Scholar
  23. 23.
    Feldmann M, Brennan FM, Maini RN (1996) Rheumatoid arthritis. Cell 85: 307Google Scholar
  24. 24.
    Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27Google Scholar
  25. 25.
    Fox SB, Moghaddam A, Westwood M, Turley H, Bicknell R, Garter KC, Harris AL (1995) Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in normal tissues: an immunohistochemical study. J Pathol 176: 183Google Scholar
  26. 26.
    Frater-Schroder M, Risau W, Hallmann R, Gautschi P, Bohlen P (1987) Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci USA 84:5277Google Scholar
  27. 27.
    Gamble JR, Vadas MA (1991) Endothelial cell adhesiveness for human T lymphocytes is inhibited by transforming growth factor-beta 1. J Immunol 146:1149Google Scholar
  28. 28.
    Gimbrone MA Jr, Leapman SB, Cotran RS, Folkman J (1972) Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 136: 261Google Scholar
  29. 29.
    Gong JH, Ratkay LG, Waterfield JD, Clark-Lewis I (1997) An antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model. J Exp Med 186: 131Google Scholar
  30. 30.
    Gotis-Graham I, Hogg PJ, McNeil HP (1997) Significant correlation between thrombospondin 1 and serine prote]vase expression in rheumatoid synovium. Arthritis Rheum 40:1780Google Scholar
  31. 31.
    Grabowski PS, Wright PK, Van `t Hof RJ, Helfrich MH, Ohshima H, Ralston SH (1997) Immunolocalization of inducible nitric oxide synthase in synovium and cartilage in rheumatoid arthritis and osteoarthritis. Br J Rheumatol 36: 651Google Scholar
  32. 32.
    Hosaka S, Akahoshi T, Wada C, Kondo H (1994) Expression of the chemokine superfamily in rheumatoid arthritis. Clin Exp Immunol 97:451Google Scholar
  33. 33.
    Hosaka S, Shah MR, Barquin N, Haines GK, Koch AE (1995) Expression of basic fibroblast growth factor and angiogenin in arthritis. Pathobiology 63: 249Google Scholar
  34. 34.
    Hu DE, Hiley CR, Fan TP (1996) Comparative studies of the angiogenic activity of vasoactive intestinal peptide, endothelins-I and -3 and angiotensin II in a rat sponge model. Br J Pharmacol 117: 545Google Scholar
  35. 35.
    Hu GF, Riordan JF, Vallee BL (1997) A putative angiogenin receptor in angiogenin-responsive human endothelial cells. Proc Natl Acad Sci USA 94:2204Google Scholar
  36. 36.
    Iruela-Arispe ML, Dvorak HF (1997) Angiogenesis: a dynamic balance of stimulators and inhibitors. Thromb Haemost 78: 672Google Scholar
  37. 37.
    Joukov V, Kaipainen A, Jettsch M, Pajusola K, Olofsson B, Kumar V, Eriksson U, Alitalo K (1997) Vascular endothelial growth factors VEGF-B and VEGF-C. J Cell Physiol 173: 211Google Scholar
  38. 38.
    Kasugai K, Job T, Kataoka H, Sasaki M, Tada T, Asai K, Kato T, Itch M (1997) Evidence for participation of gliostatin/platelet-derived endothelial cell growth factor in gastric ulcer healing. Life Sci 61: 1899Google Scholar
  39. 39.
    Koch AE, Polverini PL, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG, Stricter RM (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258: 1798Google Scholar
  40. 40.
    Koch AE, Friedman J, Burrows JC, Haines GK, Bouck NP (1993) Localization of the angiogenesis inhibitor thrombospondin in human synovial tissues. Pathobiology 61: 1Google Scholar
  41. 41.
    Koch AE, Harlow LA, Haines GK, Amento EP, Unemori EN, Wong WL, Pope RM, Ferrara N (1994) Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 152:4149Google Scholar
  42. 42.
    Koch AE, Kunkel SL, Harlow LA, Mazarakis DD, Haines GK, Burdick MD, Pope RM, Walz A, Stricter RM (1994) Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis. J Clin Invest 94: 1012Google Scholar
  43. 43.
    Koch AE, Kunkel SL, Shah MR, Hosaka S, Halloran MM, Haines GK, Burdick MD, Pope RM, Stricter RM (1995) Growth-related gene product alpha. A chemotactic cytokine for neutrophils in rheumatoid arthritis. J Immunol 155:3660Google Scholar
  44. 44.
    Koch AE, Halloran MM, Haskell CJ, Shah MR, Polverini PJ (1995) Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 376: 517Google Scholar
  45. 45.
    Koch AE, Halloran MM, Hosaka S, Shah MR, Haskell CJ, Baker SK, Panos RJ, Haines GK, Bennett GL, Pope RM, Ferrara N (1996) Hepatocyte growth factor. A cytokine mediating endothelial migration in inflammatory arthritis. Arthritis Rheum 39: 1566Google Scholar
  46. 46.
    Koolwijk P, Erck MG van, Vree WJ de, Vermeer MA, Weich HA, Hanemaaijer R, Hinsbergh VW van (1996) Cooperative effect of TNFalpha, bFGF, and VEGF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix. Role of urokinase activity. J Cell Biol 132: 1177Google Scholar
  47. 47.
    Kuruvilla AP, Shah R, Hochwald GM, Liggitt HD, Palladino MA, Thorbecke GJ (1991) Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. Proc Natl Acad Sci USA 88: 2918Google Scholar
  48. 48.
    Leibovich SJ, Polverini PJ, Shepard HM, Wiseman DM, Shively V, Nuseir N (1987) Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha. Nature 329: 630Google Scholar
  49. 49.
    Lupia E, Montrucchio G, Battaglia E, Modena V, Camussi G (1996) Role of tumor necrosis factor-α and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis. Eur J Immunol 26: 1690Google Scholar
  50. 50.
    Massague J (1990) The transforming growth factor-beta family. Annu Rev Cell Biol 6: 597Google Scholar
  51. 51.
    Mawatari M, Kohno K, Mizoguchi H, Matsuda T, Asoh K, Van Damme J, Welgus HG, Kuwano M (1989) Effects of tumor necrosis factor and epidermal growth factor on cell morphology, cell surface receptors, and the production of tissue inhibitor of metalloproteinases and IL-6 in human microvascular endothelial cells. J Immunol 143: 1619Google Scholar
  52. 52.
    McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, Wahl SM (1993) Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178: 749Google Scholar
  53. 53.
    McInnes IB, Leung BP, Field M, Wei XQ, Huang FP, Sturrock RD, Kinninmonth A, Weidner J, Mumford R, Liew FY (1996) Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients. J Exp Med 184: 1519Google Scholar
  54. 54.
    Miyasaka N, Hirata Y, Ando K, Sato K, Morita H, Shichiri M, Kanno K, Tomita K, Marumo F (1992) Increased production of endothelin-1 in patients with inflammatory arthritides. Arthritis Rheum 35: 397Google Scholar
  55. 55.
    Moenner M, Gusse M, Hatzi E, Badet J (1994) The widespread expression of angiogenin in different human cells suggests a biological function not only related to angiogenesis. Eur J Biochem 226: 483Google Scholar
  56. 56.
    Moghaddam A, Zhang HT, Fan TP, Hu DE, Lees VC, Turley H, Fox SB, Garter KC, Harris AL, Bicknell R (1995) Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci USA 92: 998Google Scholar
  57. 57.
    Montesano R, Vassalli JD, Baird A, Guillemin R, Orci L (1986) Basic fibroblast growth factor induces angiogenesis in vitro. Proc Natl Acad Sci USA 83:7297Google Scholar
  58. 58.
    Moses MA, Sudhalter J, Langer R (1990) Identification of an inhibitor of neovascularization from cartilage. Science 248: 1408Google Scholar
  59. 59.
    Muller G, Behrens J, Nussbaumer U, Bohlen P, Birchmeier W (1987) Inhibitory action of transforming growth factor beta on endothelial cells. Proc Natl Acad Sci USA 84: 5600Google Scholar
  60. 60.
    Nguyen M, Strubel NA, Bischoff J (1993) A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis. Nature 365: 267Google Scholar
  61. 61.
    Nicosia RF, Tuszynski GP (1994) Matrix-bound thrombospondin promotes angiogenesis in vitro. J Cell Biol 124:183Google Scholar
  62. 62.
    Nicosia RF, Nicosia SV, Smith M (1994) Vascular endothelial growth factor, platelet-derived growth factor, and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. Am J Pathol 145: 1023Google Scholar
  63. 63.
    Ogata H, Takeya M, Yoshimura T, Takagi K, Takahashi K (1997) The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats. J Pathol 182: 106Google Scholar
  64. 64.
    Oliver SJ, Cheng TP, Banquerigo ML, Brahn E (1995) Suppression of collagen-induced arthritis by an angiogenesis inhibitor, AGM-1470, in combination with cyclosporin: reduction of vascular endothelial growth factor (VEGF). Cell Immunol 166:196Google Scholar
  65. 65.
    Paleolog EM (1996) Angiogenesis: a critical process in the pathogenesis of RA — a role for VEGF? Br J Rheumatol 35:917Google Scholar
  66. 66.
    Paleolog EM, Hunt M, Elliott MJ, Feldmann M, Maini RN, Woody JN (1996) Deactivation of vascular endothelium by monoclonal anti-tumor necrosis factor alpha antibody in rheumatoid arthritis. Arthritis Rheum 39:1082Google Scholar
  67. 67.
    Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN (1998) Modulation of angiogenic vascular endothelial growth factor (VEGF) by TNFα and IL-1 in rheumatoid arthritis. Arthritis Rheum 41:1258Google Scholar
  68. 68.
    Pedram A, Razandi M, Hu RM, Levin ER (1997) Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. J Biol Chem 272:17097Google Scholar
  69. 69.
    Pepper MS, Montesano R, Vassalli JD, Orci L (1991) Chondrocytes inhibit endothelial sprout formation in vitro: evidence for involvement of a transforming growth factor-beta. J Cell Physiol 146: 170Google Scholar
  70. 70.
    Pepper MS, Ferrara N, Orci L, Montesano R (1992) Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesisin vitro. Biochim Biophys Res Commun 189: 824Google Scholar
  71. 71.
    Pepper MS, Vassalli JD, Orci L, Montesano R (1993) Biphasic effect of transforming growth factor-beta 1 on in vitro angiogenesis. Exp Cell Res 204: 356Google Scholar
  72. 72.
    Pertovaara L, Kaipainen A, Mustonen T, Orpana A, Ferrara N, Saksela O, Alitalo K (1994) Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J Biol Chem 269: 6271Google Scholar
  73. 73.
    Pipili-Synetos E, Sakkoula E, Maragoudakis ME (1993) Nitric oxide is involved in the regulation of angiogenesis. Br J Pharmacol 108: 855Google Scholar
  74. 74.
    Randen I, Mellbye OJ, Forte O, Natvig JB (1995) The identification of germinal centres and follicular dendritic cell networks in rheumatoid synovial tissue. Scand J Immunol 41:481Google Scholar
  75. 75.
    Remmers EF, Sano H, Lafyatis R, Case JP, Kumkumian GK, Hla T, Maciag T, Wilder RL (1991) Production of platelet derived growth factor B chain (PDGF-B/c-sis) mRNA and immunoreactive PDGF B-like polypeptide by rheumatoid synovium: coexpression with heparin binding acidic fibroblast growth factor-1. J Rheumatol 18: 7Google Scholar
  76. 76.
    Rooney M, Condell D, Quinlan W, Daly L, Whelan A, Feighery C, Bresnihan B (1988) Analysis of the histologic variation of synovitis in rheumatoid arthritis. Arthritis Rheum 31: 956Google Scholar
  77. 77.
    Rosen EM, Goldberg ID (1997) Regulation of angiogenesis by scatter factor. EXS 79: 193Google Scholar
  78. 78.
    Rubin K, Terracio L, Ronnstrand L, Heldin CH, Klareskog L (1988) Expression of platelet-derived growth factor receptors is induced on connective tissue cells during chronic synovial inflammation. Scand J Immunol 27:285Google Scholar
  79. 79.
    Salven P, Teerenhovi L, Joensuu H (1997) A high pre-treatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin's lymphoma. Blood 90:3167Google Scholar
  80. 80.
    Sano H, Forough R, Maier JA, Case JP, Jackson A, Engleka K, Maciag T, Wilder RL (1990) Detection of high levels of heparin binding growth factor-1 (acidic fibroblast growth factor) in inflammatory arthritic joints. J Cell Biol 110: 1417Google Scholar
  81. 81.
    Sano H, Engleka K, Mathem P, Hla T, Crofford LJ, Remmers EF, Jelsema CL, Goldmuntz E, Maciag T, Wilder RL (1993) Coexpression of phosphotyrosine-containing proteins, platelet-derived growth factor-B, and fibroblast growth factor-1 in situ in synovial tissues of patients with rheumatoid arthritis and Lewis rats with adjuvant or streptococcal cell wall arthritis. J Clin Invest 91: 553Google Scholar
  82. 82.
    Schlessinger J (1997) Direct binding and activation of receptor tyrosine kinases by collagen. Cell 91: 869Google Scholar
  83. 83.
    Semble EL, Turner RA, McCrickard EL (1985) Rheumatoid arthritis and osteoarthritis synovial fluid effects on primary human endothelial cell cultures. J Rheumatol 12: 237Google Scholar
  84. 84.
    Senger DR, Ledbetter SR, Claffey KP, Papadopoulos-Sergiou A, Peruzzi CA, Detmar M (1996) Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. Am J Pathol 149: 293Google Scholar
  85. 85.
    Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359: 843Google Scholar
  86. 86.
    Soncin F, Strydom DJ, Shapiro R (1997) Interaction of heparin with human angiogenin. J Biol Chem 272:9818Google Scholar
  87. 87.
    Stevens CR, Williams RB, Farrell AJ, Blake DR (1991) Hypoxia and inflammatory synovitis: observations and speculation. Ann Rheum Dis 50:124Google Scholar
  88. 88.
    Storgard CM, Stupack DG, Cheresh DA (1997) Angiogenesis inhibition with αVβ3 antagonist ameliorates early and chronic arthritis. Arthritis Rheum 40: S97Google Scholar
  89. 89.
    Usuki K, Gonez LJ, Wernstedt C, Moren A, Miyazono K, Claesson-Welsh L, Heldin CH (1994) Structural properties of 3.0 kb and 3.2 kb transcripts encoding platelet-derived endothelial cell growth factor/thymidine phosphorylase in A431 cells. Biochim Biophys Acta 1222:411Google Scholar
  90. 90.
    Waguri Y, Otsuka T, Sugimura I, Matsui N, Asai K, Moriyama A, Kato T (1997) Gliostatin/platelet-derived endothelial cell growth factor as a clinical marker of rheumatoid arthritis and its regulation in fibroblast-like synoviocytes. Br J Rheumatol 36: 315Google Scholar
  91. 91.
    Wahl SM, Allen JB, Costa GL, Wong HL, Dasch JR (1993) Reversal of acute and chronic synovial inflammation by anti-transforming growth factor beta. J Exp Med 177: 225Google Scholar
  92. 92.
    Wharton J, Rutherford RA, Walsh DA, Mapp PI, Knock GA, Blake DR, Polak JM (1992) Autoradiographic localization and analysis of endothelin-1 binding sites in human synovial tissue. Arthritis Rheum 35:894Google Scholar
  93. 93.
    Yamaguchi Y, Mann DM, Ruoslahti E, Mann DM, Yamaguchi Y, Bourdon MA, Ruoslahti E (1990) Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Analysis of glycosaminoglycan substitution in decorin by site-directed mutagenesis. Nature 346: 281Google Scholar
  94. 94.
    Yang EY, Moses HL (1990) Transforming growth factor beta 1-induced changes in cell migration, proliferation, and angiogenesis in the chicken choricallantoic membrane. J Cell Biol 111: 731Google Scholar
  95. 95.
    Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H, Kuwano M (1997) Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol 17:4015Google Scholar
  96. 96.
    Ziche M, Morbidelli L, Masini E, Amerini S, Granger HJ, Maggi CA, Geppetti P, Ledda F (1994) Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest 94: 2036Google Scholar
  97. 97.
    Ziche M, Morbidelli L, Choudhuri R, Zhang HT, Donnini S, Granger HJ, Bicknell R (1997) Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99: 2625Google Scholar

Copyright information

© Springer-Verlag 1998

Authors and Affiliations

  • Ewa M. Paleolog
    • 1
  • Roy A. Fava
    • 2
  1. 1.Kennedy Institute of RheumatologyLondonUK
  2. 2.Veterans Affairs Medical CenterWhite River JunctionUSA

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