Skip to main content
SpringerLink
Log in

The role of the inducible enzymes cyclooxygenase-2, nitric oxide synthase and heme oxygenase in angiogenesis of inflammation

  • Chapter
Inducible Enzymes in the Inflammatory Response

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

Angiogenesis, the formation of new blood vessels, is an essential part of the body’s physiology. In the non-pathological state, the process is largely quiescent and endothelial cell turnover may be measured in terms of years. However, it is an essential component of a variety of normal functions such as embryogenesis, normal tissue growth and the menstrual cycle. It also plays a role in the pathology of a variety of disease states and this led Judah Folkman, who many consider to be the “father of angiogenesis research”, to coin the term “angiogenesis-dependent disease” [1]. Some of the obvious examples which may be considered to fall into such a disease categorisation include neovascular glaucoma, hemangiomas and other tumors which need vascular support for their tissue expansion and metastatic activity. However, a number of other pathologies exist in which angiogenesis is a prominent feature; these include many of the chronic inflammatory diseases such as rheumatoid arthritis [2]. In these latter diseases, the neovasculature not only acts as a route for the increased nutrient supply required by the developing tissue, but also provides a greatly exaggerated area of activated endothelium which transmits proinflammatory signals, as well as receiving them, and allows the recruitment of large numbers of inflammatory leucocytes. The processes and cytokines involved in this proliferative capillary response have been recently reviewed [3, 4, 5]. The modulation of angiogenesis in inflammation therefore holds great therapeutic promise for the treatment of chronic inflammatory disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Folkman J (1986) How is blood vessel growth regulated in normal and neoplastic tissue. GHA Clowes Memorial Award Lecture. Cancer Res 46: 467–473

    PubMed  CAS  Google Scholar 

  2. Colville-Nash PR, Scott DL (1992) Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications. Ann Rheum Dis 51: 919–925

    Article  PubMed  CAS  Google Scholar 

  3. Colville-Nash PR, Willoughby DA (1997) Growth Factors in angiogenesis: current interest and therapeutic potential. Molecular Medicine Today 3: 14–23

    Article  PubMed  CAS  Google Scholar 

  4. Seed MP, Colville-Nash PR, Jackson JR, Winkler J (1998) Angiogenesis in inflammation. In: T-P Fan, R Auerbach (eds) The New Angiotherapy, Humana Press, USA

    Google Scholar 

  5. Seed MP (1996) Angiogenesis inhibition as a drug target for disease: An update. Exp Opin Invest Drugs 5: 1617–1637

    Article  CAS  Google Scholar 

  6. Dunn CJ, Galinet LA (1991) Angiostatic cortexone-heparin combination treatment suppresses chronic granulomatous inflammation in mice. Drug Devel Res 23: 241–248

    Google Scholar 

  7. Colville-Nash PR, El-Ghazaly M, Willoughby DA (1993) The use of angiostatic steroids to inhibit cartilage destruction in an in vivo model of granuloma mediated cartilage degradation. Agents Actions 38: 116–134

    Article  Google Scholar 

  8. Josefsson E, Tarkowski A (1997) Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol. Arth Rheum 40: 154–163

    Article  CAS  Google Scholar 

  9. Peacock DJ, Banquerigo ML, Brahn E (1995) A novel angiogenesis inhibitor suppresses rat adjuvant arthritis. Cell Immunol 160: 178–184

    Article  PubMed  CAS  Google Scholar 

  10. Peacock DJ, Banquerigo ML, Brahn E (1992) Angiogenesis inhibition suppresses collagen arthritis. J Exp Med 175: 1135–1138

    Article  PubMed  CAS  Google Scholar 

  11. Colville-Nash PR, Seed MP (1993) The current state of angiostatic therapy, with special reference to rheumatoid arthritis. Curr Opin Invest Drugs 2: 763–813

    Google Scholar 

  12. Colville-Nash PR, Seed MP, Willoughby DA (1992) Antirheumatic drugs and the development of vasculature in murine chronic granulomatous air pouches. Br J Pharmacol 107: 421P

    Google Scholar 

  13. Petersen HI (1982) Tumour angiogenesis inhibition by prostaglandin synthetase inhibitors. Anticancer Res 6: 251–253

    Google Scholar 

  14. Petersen H (1983) Effects of prostaglandin synthesis inhibitors on tumour growth and neovascularisation. Invasion Metastases 3: 151–159

    Google Scholar 

  15. Pober S, Cotran R (1990) Cytokines and endothelial cell biology. Physiol Rev 70: 427–451

    PubMed  CAS  Google Scholar 

  16. Salgardo A, Boveda JL, Monasterio J, Segura RM, Mourelle M, Gomez-Jiminez J, Per-acula R (1994) Inflammatory mediators and their influence on haemostasis. Haemosta-sis 24: 132–138

    Google Scholar 

  17. Hosaka S, Shah MR, Barquin N, Haines GK, Koch AE (1995) Expression of fibroblast growth factor and angiogenesis in arthritis. Pathobiology 63: 249–256

    Article  PubMed  CAS  Google Scholar 

  18. Lupia E, Montrucchio G, Battaglia E, Modena V, Camussi G (1996) Role of tumour necrosis factor-α and platelet activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis. Eur J Immunol 26: 1690–1694

    Article  PubMed  CAS  Google Scholar 

  19. Norrby K (1997) Interleukin-la and de novo mammalian angiogenesis. Microvasc Res 54: 58–64

    Article  PubMed  CAS  Google Scholar 

  20. Jackson JR, Minton JA, Ho ML, Wei N, Winkler JD (1997) Expression of vascular endothelial growth factor in synovial fibroblasts is induced by hypoxia and interleukin-1ß. J Rheumatol 24: 1253–1259

    PubMed  CAS  Google Scholar 

  21. Byrd V, Zhao XM, McKeehan WL, Miller GG, Thomas JW (1996) Expression and functional expansion of growth factor receptor T cells in rheumatoid synovium and peripheral blood of patients with rheumatoid arthritis. Arthritis Rheum 39: 914–922

    Article  PubMed  CAS  Google Scholar 

  22. Mapp, PI and Blake, DR (1995) Neuropeptides and the synovium. In: B Henderson, JCW Edwards, ER Pettipher (eds) Mechanisms and Models in Rheumatoid Arthritis. Academic Press, 317-333

    Google Scholar 

  23. Dusting GJ, Moncada S, Vane JR (1978) Vascular actions of arachidonic acid and its metabolites in the perfused mesenteric and femoral beds of the dog. Eur J Pharmacol 49: 65–72

    Article  PubMed  CAS  Google Scholar 

  24. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide. Physiology, pathophysiology and pharmacology. Pharmacol Rev 43: 109–142

    PubMed  CAS  Google Scholar 

  25. Maines MD (1988) Herne oxygenase: function, multiplicity, regulatory mechanisms and clinical applications. Faseb J 2: 2557–2568

    PubMed  CAS  Google Scholar 

  26. Furchgott RF, Jthianandan D (1991) Endothelium dependent and endothelium independent vasodilation involving cyclic-GMP-relaxation induced by nitric oxide, carbon monoxide, and light. Blood Vessels 28: 52–61

    PubMed  CAS  Google Scholar 

  27. Willis D, Moore AR, Frederick R, Willoughby DA (1996) Heme oxygenase: A novel target for the modulation of the inflammatory response. Nature Med 2: 87–90

    Article  PubMed  CAS  Google Scholar 

  28. Tomlinson A, Appleton I, Moore AR, Gilroy DW, Willis D, Mitchell JA Willoughby DA (1994) Cyclo-oxygenase, and nitric oxide synthase isoforms in rat carrageenin-induced pleurisy. Br J Pharm 113: 693–698

    Article  CAS  Google Scholar 

  29. Appleton I, Tomlinson A, Mitchell JA, Willoughby DA (1995) Distribution of cyclooxy-genase isoforms in murine chronic granulomatous inflammation. Implications for future anti-inflammatory therapy. J Pathol 176: 413–420.

    Article  PubMed  CAS  Google Scholar 

  30. Crofford LJ, Wilder RL, Ristimaki AP, Sano H, Remmers EF, Epps HR, Hla T (1994) Cyclooxygenase-1 and-2 expression in rheumatoid synovial tissues. Effects of inter-leukin-1ß, phorbol ester and corticosteroids. J Clin Invest 93: 1095–1101

    Article  PubMed  CAS  Google Scholar 

  31. Marok R, Winyard PG, Coumbe A, Kus ML, GaffneyK, BladesS, MappPI, MorrisCJ, BlakeDR, KaltschmidtG, BaeuerlePA (1996) Activation of the transcription factor nuclear factor-kappa B in human inflamed synovial tissue. f7d ;itArthritis Rheum} 39: 583-591

    Article  PubMed  CAS  Google Scholar 

  32. Grabowski PS, Wright PK, Van’t Hof RJ, Helrich 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: 651–655

    Article  PubMed  CAS  Google Scholar 

  33. Sakurai H, Kohsaka H, Liu MF, Higashiyama H, Hirata Y, Kanno K, Saito I, Miyasaka N (1995) Nitric oxide production and inducible nitric oxide synthase expression inflammatory arthritides. J Clin Invest 96: 2357–2363

    Article  PubMed  CAS  Google Scholar 

  34. Groszanovic Z, Gossrau R (1996) Expression of heme oxygenase-2 (HO-2)-like immunoreactivity in the rat. Acta Histochem 98: 203–214

    Article  Google Scholar 

  35. Zakhary R, Gaine SP, Dinerman JL, Ruat M, Flavahan NA, Snyder SH (1996) Heme-oxygenase-2: endothelial and neuronal localization and role in endothelium dependent relaxation. Proc Nat Acad Sci 93: 795–798

    Article  PubMed  CAS  Google Scholar 

  36. Ziche M, Jones J, GuUino PM (1982) Role of prostaglandin E1 and copper in angio-genesis. J Natl Cancer Inst 69: 475–482

    PubMed  CAS  Google Scholar 

  37. Ziehe M, Morbidelli L, Parenti A, Ledda F (1995) Nitric Oxide modulates angiogenesis elicited by prostaglandin E(1) in rabbit cornea. Adv Prostaglandin Thromboxane Res 23: 495–497

    Google Scholar 

  38. Form DM, Auerbach R (1983) PGE2 and angiogenesis. Proc Soc Exp Med 172: 214–218

    CAS  Google Scholar 

  39. Diazflores L, Gutierrez R, Valladares F, Varela H, Perez M (1994) Intense vascular sprouting from rat femoral vein induced by prostaglandins-El and E2. Anatomical Record 238: 68–76

    Article  CAS  Google Scholar 

  40. Oktsu A, Fujii K, Kurozumi S (1988) Induction of angiogenic response by chemically stable prostacyclin analogues. Prostaglandins Leukotrienes Essential Fatty Acids 33: 35–39

    Article  Google Scholar 

  41. Yamamoto T, Horikawa N, Komuro Y, Hara Y (1996) Effect of topical application of a stable prostacyclin analogue, SM-10902 on wound healing in diabetic mice. Eur J Pharmacol 302: 53–60

    Article  PubMed  CAS  Google Scholar 

  42. Lewis GP (1986) Products derived from arachidonic acid. In: GP Lewis (ed) Mediators of inflammation. Wright Publ Bristol, 44–58

    Google Scholar 

  43. Spencer-Green G, Caulkins KM (1993) Augmentation of interleukin-1 induced prostacyclin production by endothelial cell growth factor: Implications for chronic synovitis. Prostaglandins 45: 439–445

    Article  PubMed  CAS  Google Scholar 

  44. Pankonin G, Teuscher E (1991) Stimulation of endothelial cell migration by thrombin. Biomed Biochim Acta 50: 1073–1078

    PubMed  CAS  Google Scholar 

  45. Ziche M, Morbidelli L, Choudhuri R, Zhang H-T, Donnini S, Granger, H, Bicknell (1997) Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99: 2625–2634

    Article  PubMed  CAS  Google Scholar 

  46. Nagashima M, Yoshino S, Ishiwata T, Asano G (1995) Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis. J Rheumatol 22: 1624–1630

    PubMed  CAS  Google Scholar 

  47. Fava RA, Olsen NJ, Spencer-Green G, Yeo KT, Berse B, Jackman RW, Senger DR, Dvorak HE, Brown LF (1994) Vascular permeability factor/endothelial growth factor (VPR/ VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med 180: 341–346

    Article  PubMed  CAS  Google Scholar 

  48. Koch AE, Harlow LA, Haines GK, Amento EP, Unemori EN, Wong WL, Pope RM, Fer-rarra N (1994) Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. Immunol 152: 4149–4156

    CAS  Google Scholar 

  49. Ben-AV P, Crofford LJ, Wilder RL, Hla T (1995) Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis. FEBS Lett 372: 83–7

    Article  PubMed  CAS  Google Scholar 

  50. Morbidelh L, Chang CH, Douglas JG, Granger HJ, Ledda F, Ziche M (1996) Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium. Am J Physiol 39: H411–H415

    Google Scholar 

  51. Ziehe M, Parenti A, Ledda F, Dell’era P, Granger HJ, Maggi CA, Presta M (1997) Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF. Circ Res 80(6): 845–852

    Article  Google Scholar 

  52. Tiefenbacher CP, Chilian WM (1997) Basic fibroblast growth factor and heparin influence coronary arteriolar tone by causing endothelium dependent dilation. Cardiovasc Res 34: 411–417

    Article  CAS  Google Scholar 

  53. Fujii E, Ire K, Ohba K, Ogawa A, Yoshioka T, Yamakawa M (1997) Role of nitric oxide, prostaglandins and tyrosine kinase in vascular endothelial growth factor-induced increase in vascular permeability in mouse skin. Naunyn Schmiedebergs Arch Pharmacol 356: 475–480

    Article  PubMed  CAS  Google Scholar 

  54. van der Zee R, Murohara T, Luo ZY, ZoUmann F, Passed J, Lekutat C, Isner JM (1997) Vascular endothelial growth factor vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation 95: 1030–1037

    Article  PubMed  Google Scholar 

  55. Ziche M, Morbidelli L, Masini E, Amerini S, Granger HJ, Maggi CA, Geppeti 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: 2036–2044

    Article  PubMed  CAS  Google Scholar 

  56. Leibovitch SJ, Polverini PJ, Fong TW, Harlow LA, Koch AE (1994) Production of angiogenic activity by human monocytes requires an 1-arginine nitric oxide synthase-depen-dent effector. Proc Natl Acad Sci USA 91: 4190–4194

    Article  Google Scholar 

  57. Konturek SJ, Brzozowski T, Majika J, Purko-Polonczyk J, Stachuro J (1993) Inhibition of nitric oxide synthase delays healing of chronic gastric ulcers. Eur J Pharmacol 239: 215–217

    Article  PubMed  CAS  Google Scholar 

  58. Jenkins DC, Charles IG, Thomsen LL, Moss DW, Holmes LA, Bayliss SA, Rhodes P, Westmore K, Emson PC, Moncada S (1995) Roles of nitric oxide in tumour growth. Proc Natl Acad Sci USA 92: 4392–4396

    Article  PubMed  CAS  Google Scholar 

  59. Mellilo G, Musso T, Sica A, Taylor LS, Cox GW, Varesio LA (1995) A Hypoxia-respon-sive element mediates a novel pathway of activation of the inducible nitric oxide promoter. J Exp Med 182: 1683–1693

    Article  Google Scholar 

  60. Schneemann M, Schoeden G, Frei K, Schaffner A (1993) Immuno vascular communication: Activation and deactivation of murine endothelial cell nitric oxide synthase by cytokines. Immunol Lett 35: 159–162

    Article  PubMed  CAS  Google Scholar 

  61. Murata J, Corradin SB, Felley-Bosco E, Juillerat-Jeanneret L (1995) Involvement of a transforming growth factor beta-like molecule in tumour cell derived inhibition of nitric oxide synthesis in cerebral endothelial cells. Int J Cancer 61: 743–748

    Article  Google Scholar 

  62. Kanno K, Hirata Y, Imai T, Iwashina M, Marumo F (1994) Regulation of inducible nitric oxide synthase gene by interleukin-1 beta in rat vascular endothelial cells. Am J Physiol 267: H2318–2324

    PubMed  CAS  Google Scholar 

  63. Ungureanu-Longrois D, Ballingand JL, Simmons WW, Okada I, Kobzik L, Lowenstein CJ, Kunkel SL, Michel T, Kelly RA, Smith TW (1995) Induction of nitric oxide synthase activity by cytokines in ventricular myocytes is necessary but not sufficient to decrease contractile responsiveness to beta adrenergic agonists. Circ Res 11: 494–502

    Article  Google Scholar 

  64. Inoue N, Venema RC, Sayegh HS, Ohara Y, Murphy TJ, Harrison DG (1995) Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor betal. Arterioscler Thromb Vase Biol 15: 1255–1261

    Article  CAS  Google Scholar 

  65. Yang EY, Moses HL (1990) Transforming growth factor beta 1-induced changes in cell migration, proliferation and angiogenesis in the chicken chorioallantoic membrane. J Cell Biol 111: 131–141

    Article  Google Scholar 

  66. Fiegel VD, Knighton DR (1988) Transforming growth factor beta causes indirect angiogenesis by recruiting monocytes. FASEB J 137: 295–302.

    Google Scholar 

  67. Pipili-Synetos E, Sakkoula E, Haralabopoulos G, Andriolopoulou, Peristeris P, Maragoudakis ME (1994) Evidence that nitric oxide is an endogenous antiangiogenic mediator. Br J Pharmacol 111: 894–902

    Article  PubMed  CAS  Google Scholar 

  68. Pipili-Synetos E, Papageorgiou A, Sotiropolou G, Fotsis T, Karaliulakis G, Maragoudakis ME (1995) Inhibition of angiogenesis, tumour growth and metastasis by the NO-releasing vasodilators, isosorbide mononitrate and dinitrate. Br J Pharmacol 116: 1829–1834

    Article  PubMed  CAS  Google Scholar 

  69. Sakkouia E, Pipili-Synetos E, Maragoudakis ME (1997) Involvement of nitric oxide in the inhibition of angiogenesis by interleukin-2. Br J Pharmacol 122: 793–795

    Article  Google Scholar 

  70. Montrucchio G, Lupia E, DeMartino A, Battaglia E, Arese M, Tizzani A, Bussolino F, Camussi G (1997) Nitric oxide mediates angiogenesis induced in vivo by platelet activating factor and by tumour necrosis factor-α. Am J Pathol 151: 557–563

    PubMed  CAS  Google Scholar 

  71. Spisni E, Manica F, Tomasi V (1992) Involvement of prostanoids in the regulation of angiogenesis by polypeptide growth factors. Prostaglandins & Essential Patty Acids 47: 111–115

    Article  CAS  Google Scholar 

  72. Moatter TM, Gerritsen ME (1994) Fibroblast growth factor upregulates PGG/H synthase in rabbit microvascular endothelial cells by a glucocorticoid independent mechanism. J Cell Physiol 151: 571–578

    Article  Google Scholar 

  73. Moatter TM, Gerritsen ME (1994) Acidic fibroblast growth factor induction of cyclooxygenase-2 in rabbit cardiac muscle microvessel endothelial cells: mediation by protein kinase C. Microcirculation 1: 79–88

    Article  PubMed  CAS  Google Scholar 

  74. Davidge ST, Baker PN, Laughlin MK, Roberts JM (1995) Nitric oxide produced by endothelial cells increases production of eicosanoids through activation of prostaglandin H synthase. Circ Res 77: 274–283

    Article  PubMed  CAS  Google Scholar 

  75. DeCatarina R, Dorso C, Tack-Goldman K, Weksler B (1985) Nitrates and endothelial prostacyclin production. Circulation 71: 176–182

    Article  Google Scholar 

  76. Levin R, Jaffe E, Weksler B, Tack-Goldman K (1981) Nitroglycerin stimulates synthesis of prostacyclin by cultured endothelial cells. J Clin Invest 67: 762–769

    Article  PubMed  CAS  Google Scholar 

  77. Chaudhury AR, Frischer H, Malik AB (1996) Inhibition of endothehal cell proliferation and bFGF-induced phenotypic modulation by nitric oxide. J Cell Biochem 63: 125–134

    Article  Google Scholar 

  78. Liu Y, Cox SR, Morita T, Kourembanas S (1991) Hypoxia regulates VEGF gene expression in endothelial cells: Identification of a 5’ enhancer. Circ Res 77: 635–643

    Google Scholar 

  79. Lee PJ, Jiang B-H, Chin BY, Iyer NV, Alam J, Semenza GL, Choi AMK (1997) Hypoxia inducible factor mediates transcriptional activation of the heme oxygenase gene in response to hypoxia. J Biol Chem 272(9): 5375–5381

    Article  PubMed  CAS  Google Scholar 

  80. Abraham NG, Lavrosky Y, Schwartzman ML, Stoltz RA, Levere RD, Gerritsen ME, Shibahara S, Kappas A (1995) Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity. Proc Natl Acad Sci USA 92: 6798–6802

    Article  PubMed  CAS  Google Scholar 

  81. Deramaudt BM, Braunstein S, Remy P, Abraham NG (1998) Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis. J Cell Biochem 68(1): 121–127

    Article  PubMed  CAS  Google Scholar 

  82. Kourembanas S, Morita T, Liu Y, Christou H (1997) Mechanisms by which oxygen regulates gene expression and cell-cell interaction in the vasculature. Kidney Int 51: 438–443

    Article  PubMed  CAS  Google Scholar 

  83. Yee EL, Pitt BR, Billiar TR, Kim YM (1996) Effect of nitric oxide on heme-metabolism in pulmonary artery endothelial cells. Am J Physiol 271: L512–518

    PubMed  CAS  Google Scholar 

  84. Foresti R, Clarke JE, Green CJ, Motterlini R (1997) Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells. Involvement of superoxide and peroxynitrite anions. J Biol Chem 272: 18411–18417

    Article  PubMed  CAS  Google Scholar 

  85. Seki T, Naruse M, Yoshimoto T, Tanabe A, Imaki T, Hagiwara H, Hirose S, Demura H (1997) Interrelation between nitric oxide synthase and heme oxygenase in rat endothelial cells. Eur J Pharmacol 331: 87–91

    Article  PubMed  CAS  Google Scholar 

  86. Thompson WD, Harvey JA, Kazmi MA, Stout AJ (1991) Fibrinolysis and angiogenesis in wound healing. J Pathol 165: 311–318

    Article  PubMed  CAS  Google Scholar 

  87. Willis. D. (1995) Expression and modulatory effects of heme oxygenase in acute inflammation in the rat. Inflammation Res 44(S2): S218–S220

    Article  CAS  Google Scholar 

  88. Kibbey MC, Grant DS, Kleinman UK (1992) Role of SIKVAV site of laminin in promotion of angiogenesis and tumour growth-An in vivo matrigel model. J Natl Cancer Inst 84: 1663–1638.

    Article  Google Scholar 

  89. Kowalski J, Kwan HH, Prionas SD, Allison AC, Fajardo LF (1992) Characterization of the disc angiogenesis system. Exp Mol Pathol 56: 1–19

    Article  PubMed  CAS  Google Scholar 

  90. Jakobsson AE, Norrby K, Ericsson LE (1994) A morphometric method to evaluate angiogenesis kinetics in the rat mesentry. Int J Exp Pathol 25: 219–224

    Google Scholar 

  91. Ausprunk DH, Knighton DR, Folkman J (1974) Differentiation of vascular endothelium in the chick chorioallantois: a structural and autoradiographic study. Dev Biol 38: 237–248

    Article  PubMed  CAS  Google Scholar 

  92. Kimura M, Amemiya K, Yamada T, Suzuki J (1986) Quantitative method for measuring adjuvant-induced granuloma angiogenesis in insulin-treated diabetic mice. J Pharmaco-hiodyn 9: 442–446

    Article  CAS  Google Scholar 

  93. Colville-Nash PR, Alam CAS, Appleton I, Brown JR, Seed MP, Willoughby DA (1995) The Pharmacological modulation of angiogenesis in chronic granulomatous inflammation. J Pharmacol Exp Ther 274: 1463–1472

    PubMed  CAS  Google Scholar 

  94. Orlandi C, Dunn CJ, Cutshaw LG (1988) Evaluation of angiogenesis in chronic inflammation by laser-Doppler flowmetry. Clin Sci 74: 119–121

    PubMed  CAS  Google Scholar 

  95. Andrade SP, Fan T-P, Lewis GP (1987) Quantitative studies on angiogenesis in a rat sponge model. Br J Exp Path 68: 755–766

    CAS  Google Scholar 

  96. Frucht J, Zauberman H (1984) Topical indomethacin effect on neovascularization of the cornea and on prostaglandin E2 levels. Br J Ophthalmol 68: 656–659

    Article  PubMed  CAS  Google Scholar 

  97. Majima M, Isono M, Ikeda Y, Hayashi I, Hatanaka K, Harada Y, Katsumata O, Yamashina S, Katori M, Yamamoto S (1997) Significant roles of inducible cyclooxyge-nase (COX)-2 in angiogenesis in rat sponge implants. Jpn J Pharmacol 75(2): 105–114

    Article  PubMed  CAS  Google Scholar 

  98. Colville-Nash PR, Seed MP, Willoughby DA (1992) Antirheumatic Drugs and the development of vasculature in murine chronic granulomatous air pouches. Br J Pharmacol 107: 421P

    Google Scholar 

  99. Bevilacqua M, Magni E (1993) Recent contributions to knowledge of the mechanism of action of nimesulide. Drugs 46 (S1): 40–47

    Article  PubMed  CAS  Google Scholar 

  100. Famaey JP (1997) In vitro and in vivo pharmacological evidence of selective cyclooxygenase-2 inhibition by nimesulide: An overview. Inflamm Res 46: 437–446

    Article  PubMed  CAS  Google Scholar 

  101. Gilroy D, Tomlinson A, Willoughby DA (1998) Differential effects of inhibition of isoforms of cyclooxygenase (COX-1, COX-2) in chronic inflammation. Inflamm Res 47: 79–85

    Article  PubMed  CAS  Google Scholar 

  102. Maffei FR, Carini M, Aldini G, Saibene L, Macciocchi A (1993) Antioxidant profile of nimesulide, indomethacin and diclofenac in phosphatidyl choline liposomes (PCL) as membrane model. Int J Tiss React XV: 225–234

    Google Scholar 

  103. Maffei FR, Carini M, Aldini G, Saibene L, Morelli R (1995) Differential inhibition of superoxide, hydroxyl and peroxyl radicals by nimesulide and its main metabolite 4-hydroxynimesulide. Arneimittelforschung 45: 1102–1109

    Google Scholar 

  104. Rufer C, Schillinger E, Middleton J, Pons F, Rabeck C, Thierer K, Wintle J, Wolff B, Zsak M, Dukor P (1996) Some aspects of IL-8 pathophysiology. III: Chemokine interaction with endothelial cells. J Leukocyte Biol 31: 3591–3596

    Google Scholar 

  105. Alam CAS, Seed MP, Willoughby DA (1995) Angiostasis and vascular regression in chronic granulomatous inflammation induced by diclofenac in combination with Hyaluronan. J Pharm Pharmacol 47: 407–411

    Article  PubMed  CAS  Google Scholar 

  106. Alam CAS, Seed MP, Willoughby DA (1995) Angiostasis and vascular regression in chronic granulomatous inflammation induced by diclofenac in combination with hyaluronan (HYAL CT-1101). Annals Rheum Dis 54: 777

    Google Scholar 

  107. Seed MP, Alam CAS, Willoughby DA (1995) Regression of granulomatous tissue neo-vasculature with angiostatic steroid therapy. Annals Rheum Dis 54: 777

    Google Scholar 

  108. Brown MB, Marriott C, Martin GP (1995) The effect of hyaluronan on the in vitro deposition of diclofenac within the skin. Int J Tiss React XVII: 133–140

    Google Scholar 

  109. Brown MB, Bennett F, Marriott C, Martin GP (1996) Hyaluronan: a transdermaldrug delivery system. An in vitro investigation. Prog Rheumatol VI: 59–63

    Google Scholar 

  110. Papworth J, Seed MP, Willoughby DA (1996) Resident granulomatous tissue and tumour prostaglandin synthesis inhibition by topical diclofenac in hyaluronan (HYAL EX-0001). Roy Soc Med Round Table Ser 45: 54–58

    CAS  Google Scholar 

  111. Colville-Nash PR, Clarke AE, Sy-Yed, Gilroy DW, Paul-Clark M, Tomhnson A, Willoughby DA (1996) Control of inducible nitric oxide synthase in murine macrophages by diclofenac and hyaluronic acid. Royal Soc Med Round Table Ser 45: 127–146

    CAS  Google Scholar 

  112. Appleton I, Brown NJ, Willis D, Colville-Nash PR, Alam CAS, Brown JR, Willoughby DA (1996) The role of vascular endothelial growth factor in a murine granulomatous tissue air pouch model of angiogenesis. J Pathol 180: 90–94

    Article  PubMed  CAS  Google Scholar 

  113. Handy RL, Wallacw P, Moore PK (1996) Inhibition of nitric oxide synthase by isoth-ioureas: cardiovascular and anti-nociceptive effects. Pharmacol Biochem Behav 55: 179–184

    Article  PubMed  CAS  Google Scholar 

  114. Najafipour H, Ferrell WR (1993) Nitric oxide modulates sympathetic vasoconstriction and basal blood flow in normal and healthy inflamed rabbit knee joints. Exp Physiol 78 (5): 615–624

    PubMed  CAS  Google Scholar 

  115. Ridger VC, Pettipher ER, Bryant CE, Brain SD (1997) Effect of nitric oxide synthase inhibitors aminoguanidine and L-N6-(1-iminoethyl)lysine on zymosan-induced plasma extravsation in rat skin. J Immunol 159: 383–390

    PubMed  CAS  Google Scholar 

  116. Griffiths MJ, Messent M, MacAllister RJ, Evans TW (1993) Aminoguanidine selectively inhibits iNOS synthesis. Br J Pharmacol 110: 963–1604

    Article  PubMed  CAS  Google Scholar 

  117. Seed MP, Brown JR, Freemantle CN, Papworth JL, Colville-Nash PR, Willis D, Somerville KW, Asculai S, Willoughby DA (1997) The inhibition of colon-26 adenocarcinoma development and angiogenesis by topical diclofenac in 2.5% hyaluronan. Cancer Res 57: 1625–1629

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Michael P. Seed

    Present address: Paneutics Ltd., P.O. Box 1358, Swindon, SN3 4GP, UK

Authors and Affiliations

  1. Experimental Pathology, William Harvey Research Institute, Saint Bartholomew’s, Charterhouse Square, London, EC1M 6BQ, UK, PO. Box 1358, Swindon SN3 4GP, UK

    Michael P. Seed, Derek Gilroy, Mark Paul-Clark, Paul R. Colville-Nash, Dean Willis, Annette Tomlinson & Derek A. Willoughby

  2. The Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK

    Michael P. Seed, Derek Gilroy, Mark Paul-Clark, Paul R. Colville-Nash, Dean Willis, Annette Tomlinson & Derek A. Willoughby

Authors
  1. Michael P. Seed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derek Gilroy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark Paul-Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul R. Colville-Nash
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dean Willis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Annette Tomlinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Derek A. Willoughby
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Experimental Pathology, St. Bartholomew’s and The Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK

    Derek A. Willoughby  & Annette Tomlinson  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Basel AG

About this chapter

Cite this chapter

Seed, M.P. et al. (1999). The role of the inducible enzymes cyclooxygenase-2, nitric oxide synthase and heme oxygenase in angiogenesis of inflammation. In: Willoughby, D.A., Tomlinson, A. (eds) Inducible Enzymes in the Inflammatory Response. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8747-2_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-8747-2_6

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9755-6

  • Online ISBN: 978-3-0348-8747-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation