Skip to main content

Advertisement

Log in

Angiogenesis and chronic inflammation: cause or consequence?

  • Review Paper
  • Published:
Angiogenesis Aims and scope Submit manuscript

Abstract

Evidence has been gathered regarding the association between angiogenesis and inflammation in pathological situations. These two phenomena have long been coupled together in many chronic inflammatory disorders with distinct etiopathogenic origin, including psoriasis, rheumatoid arthritis, Crohn’s disease, diabetes, and cancer. Lately, this concept has further been substantiated by the finding that several previously established non-inflammatory disorders, such as osteoarthritis and obesity, display both inflammation and angiogenesis in an exacerbated manner. In addition, the interplay between inflammatory cells, endothelial cells and fibroblasts in chronic inflammation sites, together with the fact that inflammation and angiogenesis can actually be triggered by the same molecular events, further strengthen this association. Therefore, elucidating the underlying cellular and molecular mechanisms that gather together the two processes is mandatory in order to understand their synergistic effect, and to develop new therapeutic approaches for the management of these disorders that cause a great deal of discomfort, disability, and in some cases death.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Benelli R, Lorusso G, Albini A, Noonan DM (2006) Cytokines and chemokines as regulators of angiogenesis in health and disease. Curr Pharm Des 12:3101–3115

    Article  PubMed  CAS  Google Scholar 

  2. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621

    Article  PubMed  CAS  Google Scholar 

  3. Charo IF, Taubman MB (2004) Chemokines in the pathogenesis of vascular disease. Circ Res 95:858–866

    Article  PubMed  CAS  Google Scholar 

  4. Coussens L, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed  CAS  Google Scholar 

  5. Carmeliet P (2005) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395

    Article  CAS  Google Scholar 

  6. Bonnet CS, Walsh DA (2005) Osteoarthritis, angiogenesis and inflammation. Rheumatology (Oxford) 44:7–16

    Article  CAS  Google Scholar 

  7. Lusis AJ (2000) Atherosclerosis. Nature 407:233–241

    Article  PubMed  CAS  Google Scholar 

  8. Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347–355

    Article  PubMed  CAS  Google Scholar 

  9. Wubben DP, Adams AK (2006) Metabolic syndrome: what’s in a name? WMJ 105:17–20

    PubMed  Google Scholar 

  10. Tan TT, Coussens L (2007) Humoral immunity, inflammation and cancer. Curr Opin Immunol 19:1–8

    Article  CAS  Google Scholar 

  11. Ishida S, Usui T, Yamashiro K et al (2003) VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J Exp Med 198:483–489

    Article  PubMed  CAS  Google Scholar 

  12. Otani A, Takagi H, Oh H et al (1999) Expression of angiopoietins and Tie2 in human choroidal neovascular membranes. Invest Ophthalmol Vis Sci 40:1912–1920

    PubMed  CAS  Google Scholar 

  13. Nathan C (2002) Points of control in inflammation. Nature 420:846–852

    Article  PubMed  CAS  Google Scholar 

  14. Philip M, Rowley DA, Schreiber H (2004) Inflammation as a tumor promoter in cancer induction. Semin Cancer Biol 14:433–439

    Article  PubMed  CAS  Google Scholar 

  15. Visser K, Eichten A, Coussens L (2006) Paradoxical roles of the immune system during cancer development. Nat Cancer Rev 6:24–37

    Article  CAS  Google Scholar 

  16. Tracey KJ (2002) The inflammatory reflex. Nature 420:853–859

    Article  PubMed  CAS  Google Scholar 

  17. Beaudeux JL, Giral P, Bruckert E et al (2004) Matrix metalloproteinases, inflammation and atherosclerosis: therapeutic perspectives. Clin Chem Lab Med 42:121–131

    Article  PubMed  CAS  Google Scholar 

  18. Mrowietz U, Boehncke WH (2006) Leukocyte adhesion: a suitable target for anti-inflammatory drugs. Curr Pharm Des 12:2825–2831

    Article  PubMed  CAS  Google Scholar 

  19. Baynes J, Dominiczak M (eds) (2005) Medical biochemistry. Blackwell, London

    Google Scholar 

  20. Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936

    Article  PubMed  CAS  Google Scholar 

  21. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257

    Article  PubMed  CAS  Google Scholar 

  22. Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31

    Article  PubMed  CAS  Google Scholar 

  23. Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364

    Article  PubMed  CAS  Google Scholar 

  24. Asahara T, Masuda H, Takahashi T et al (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228

    PubMed  CAS  Google Scholar 

  25. Lyden D, Hattori K, Dias S et al (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7:1194–1101

    Article  PubMed  CAS  Google Scholar 

  26. Costa C (2006) Influence of angiogenic factors and bone marrow-derived endothelial/hematopoietic cells in the growth of solid tumors. Crit Rev Oncog 12:157–160

    Google Scholar 

  27. Yancopoulos GD, Davis S, Gale NW et al (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242–248

    Article  PubMed  CAS  Google Scholar 

  28. Presta M, Dell’Era P, Mitola S et al (2005) Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 16:159–178

    Article  PubMed  CAS  Google Scholar 

  29. Miyazono K, Usuki K, Heldin CH (1991) Platelet-derived endothelial cell growth factor. Prog Growth Factor Res 3:207–217

    Article  PubMed  CAS  Google Scholar 

  30. Ohnishi T, Daikuhara Y (2003) Hepatocyte growth factor/scatter factor in development, inflammation and carcinogenesis: its expression and role in oral tissues. Arch Oral Biol 48:797–704

    Article  PubMed  CAS  Google Scholar 

  31. Luttun A, Tjwa M, Carmeliet P (2002) Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders. Ann N Y Acad Sci 979:80–93

    Article  PubMed  CAS  Google Scholar 

  32. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  PubMed  CAS  Google Scholar 

  33. Wheeler-Jones C, Abu-Ghazaleh R, Cospedal R et al (1997) Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42/p44 mitogen-activated protein kinase. FEBS Lett 420:28–32

    Article  PubMed  CAS  Google Scholar 

  34. Gerber HP, McMurtrey A, Kowalski J et al (1998) Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 273:30336–30343

    Article  PubMed  CAS  Google Scholar 

  35. Gerber HP, Dixit V, Ferrara N (1998) Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 273:13313–13316

    Article  PubMed  CAS  Google Scholar 

  36. Asahara T, Takahashi T, Masuda H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972

    Article  PubMed  CAS  Google Scholar 

  37. Costa C, Soares R, Schmitt F (2004) Angiogenesis: now and then. APMIS 112:402–412

    Article  PubMed  Google Scholar 

  38. Soares R, Guo S, Russo J et al (2003) Role of the estrogen antagonist ICI 182,780 in vessel assembly and apoptosis of endothelial cells. Ultrastruct Pathol 27:33–39

    Article  PubMed  Google Scholar 

  39. Soares R, Guo S, Gartner F et al (2003) 17 beta-estradiol-mediated vessel assembly and stabilization in tumor angiogenesis requires TGF beta and EGFR crosstalk. Angiogenesis 6:271–281

    Article  PubMed  CAS  Google Scholar 

  40. Soares R, Balogh G, Guo S et al (2004) Evidence for the notch signaling pathway on the role of estrogen in angiogenesis. Mol Endocrinol 18:2333–2343

    Article  PubMed  CAS  Google Scholar 

  41. Costa C, Soares R, Reis-Filho JS et al (2002) Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J Clin Pathol 55:429–434

    PubMed  CAS  Google Scholar 

  42. Murdoch C, Muthana M, Lewis CE (2005) Hypoxia regulates macrophage functions in inflammation. J Immunol 175:6257–6263

    PubMed  CAS  Google Scholar 

  43. Semenza GL, Shimoda LA, Prabhakar NR (2006) Regulation of gene expression by HIF-1. Novartis Found Symp 272:2–8

    PubMed  CAS  Google Scholar 

  44. Kreis T, Vale R (1999) Guidebook to the extracellular matrix, anchor, and adhesion proteins. Wiley, New York

    Google Scholar 

  45. Ley K (2001) Pathways and bottlenecks in the web of inflammatory adhesion molecules and chemoattractants. Immunol Res 24:87–95

    Article  PubMed  CAS  Google Scholar 

  46. Johnson BA, Haines GK, Harlow LA et al (1993) Adhesion molecule expression in human synovial tissue. Arthritis Rheum 36:137–146

    PubMed  CAS  Google Scholar 

  47. Danese S, Sans M, de la MC et al (2006) Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 130:2060–2073

    Article  PubMed  CAS  Google Scholar 

  48. Naldini A, Carraro F (2005) Role of inflammatory mediators in angiogenesis. Curr Drug Targets Inflamm Allergy 4:3–8

    Article  PubMed  CAS  Google Scholar 

  49. Gong R, Rifai A, Dworkin LD (2006) Anti-inflammatory effect of hepatocyte growth factor in chronic kidney disease: targeting the inflamed vascular endothelium. J Am Soc Nephrol 17:2464–2473

    Article  PubMed  CAS  Google Scholar 

  50. Funa K, Uramoto H (2003) Regulatory mechanisms for the expression and activity of platelet-derived growth factor receptor. Acta Biochim Pol 50:647–658

    PubMed  CAS  Google Scholar 

  51. Lee YC (2005) The involvement of VEGF in endothelial permeability: a target for anti-inflammatory therapy. Curr Opin Invest Drugs 6:1124–1130

    CAS  Google Scholar 

  52. Maxwell PH, Wiesener MS, Chang GW et al (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275

    Article  PubMed  CAS  Google Scholar 

  53. Karin M, Cao Y, Greten FR et al (2002) NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310

    Article  PubMed  CAS  Google Scholar 

  54. Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441:431–436

    Article  PubMed  CAS  Google Scholar 

  55. Pacifico F, Leonardi A (2006) NF-kappaB in solid tumors. Biochem Pharmacol 272:1142–1152

    Article  CAS  Google Scholar 

  56. Nam NH (2006) Naturally occurring NF-kappaB inhibitors. Mini Rev Med Chem 6:945–951

    Article  PubMed  CAS  Google Scholar 

  57. Fiedler U, Reiss Y, Scharpfenecker M et al (2006) Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 12:235–239

    Article  PubMed  CAS  Google Scholar 

  58. Mouta C, Heroult M (2003) Inflammatory triggers of lymphangiogenesis. Lymphat Res Biol 1:201–218

    Article  PubMed  CAS  Google Scholar 

  59. Creamer D, Sullivan D, Bicknell R et al (2002) Angiogenesis in psoriasis. Angiogenesis 5:231–236

    Article  PubMed  CAS  Google Scholar 

  60. Plant D, Young HS, Watson RE et al (2006) The CX3CL1-CX3CR1 system and psoriasis. Exp Dermatol 15:900–903

    Article  PubMed  CAS  Google Scholar 

  61. Schon MP, Ludwig RJ (2005) Lymphocyte trafficking to inflamed skin-molecular mechanisms and implications for therapeutic target molecules. Expert Opin Ther Targets 9:225–243

    Article  PubMed  Google Scholar 

  62. Lowes MA, Chamian F, Abello MV et al (2005) Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc Natl Acad Sci USA 102:19057–19062

    Article  PubMed  CAS  Google Scholar 

  63. Creamer D, Allen M, Sousa A et al (1995) Altered vascular endothelium integrin expression in psoriasis. Am J Pathol 147:1661–1667

    PubMed  CAS  Google Scholar 

  64. Yonekawa K, Harlan JM (2005) Targeting leukocyte integrins in human diseases. J Leukoc Biol 77:129–140

    Article  PubMed  CAS  Google Scholar 

  65. Nickoloff BJ, Bonish BK, Marble DJ et al (2006) Lessons learned from psoriatic plaques concerning mechanisms of tissue repair, remodeling, and inflammation. J Invest. Dermatol 126(Suppl):16

    Google Scholar 

  66. Pastore S, Mascia F, Mariotti F et al (2004) Chemokine networks in inflammatory skin diseases. Eur J Dermatol 14:203–208

    PubMed  CAS  Google Scholar 

  67. Nielsen HJ, Christensen IJ, Svendsen MN et al (2002) Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis. Inflamm Res 51:563–567

    Article  PubMed  CAS  Google Scholar 

  68. Detmar M, Brown LF, Claffey KP et al (1994) Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180:1141–1146

    Article  PubMed  CAS  Google Scholar 

  69. Detmar M (2000) The role of VEGF and thrombospondins in skin angiogenesis. J Dermatol Sci 24(Suppl 1):S78–S84

    Article  PubMed  CAS  Google Scholar 

  70. Cordiali-Fei P, Trento E, D’Agosto G et al (2006) Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-alpha. J Autoimmune Dis 5:3–5

    Google Scholar 

  71. Xia YP, Li B, Hylton D et al (2003) Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis. Blood 102:161–168

    Article  PubMed  CAS  Google Scholar 

  72. Hernandez GL, Volpert OV, Iniguez MA et al (2001) Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2. J Exp Med 193:607–620

    Article  PubMed  CAS  Google Scholar 

  73. Shear NH, Langley RG, Ho V (2006) Efalizumab, a reversible T-cell modulator for psoriasis. J Cutan Med Surg 9(Suppl 1):4–9

    PubMed  Google Scholar 

  74. Numerof RP, Dinarello CA, Asadullah K (2005) Cytokines as potential therapeutic targets for inflammatory skin diseases. Eur Cytokine Netw 16:101–103

    PubMed  CAS  Google Scholar 

  75. Bainbridge J, Sivakumar B, Paleolog E (2006) Angiogenesis as a therapeutic target in arthritis: lessons from oncology. Curr Pharm Des 12:2631–2644

    Article  PubMed  CAS  Google Scholar 

  76. Vergunst CE, van der Sande MG, Lebre MC et al (2005) The role of chemokines in rheumatoid arthritis and osteoarthritis. Scand J Rheumatol 34:415–425

    Article  PubMed  CAS  Google Scholar 

  77. Smith MD, Barg E, Weedon H et al (2003) Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints. Ann Rheum Dis 62:303–307

    Article  PubMed  CAS  Google Scholar 

  78. Paleolog EM (2002) Angiogenesis in rheumatoid arthritis. Arthritis Res 4(Suppl 3):S81–S90

    Article  PubMed  Google Scholar 

  79. Paleolog EM, Fava RA (1998) Angiogenesis in rheumatoid arthritis: implications for future therapeutic strategies. Semin Immunopathol 20:73–94

    Article  CAS  Google Scholar 

  80. Rooney M, Condell D, Quinlan W et al (1988) Analysis of the histologic variation of synovitis in rheumatoid arthritis. Arthritis Rheum 31:956–963

    Article  PubMed  CAS  Google Scholar 

  81. Walsh DA (1999) Angiogenesis and arthritis. Rheumatology 38:103–112

    Article  PubMed  CAS  Google Scholar 

  82. Etherington PJ, Winlove P, Taylor P et al (2002) VEGF release is associated with reduced oxygen tensions in experimental inflammatory arthritis. Clin Exp Rheumatol 20:799–805

    PubMed  CAS  Google Scholar 

  83. Maruotti N, Crivellato E, Cantatore FP et al (2007) Mast cells in rheumatoid arthritis. Clin Rheumatol 26:1–4

    Article  PubMed  Google Scholar 

  84. Smolen JS, Redlich K, Zwerina J et al (2005) Pro-inflammatory cytokines in rheumatoid arthritis: pathogenetic and therapeutic aspects. Clin Rev Allergy Immunol 28:239–248

    Article  PubMed  CAS  Google Scholar 

  85. Karouzakis E, Neidhart M, Gay RE et al (2006) Molecular and cellular basis of rheumatoid joint destruction. Immunol Lett 106:8–13

    Article  PubMed  CAS  Google Scholar 

  86. Perper SJ, Browning B, Burkly LC et al (2006) TWEAK is a novel arthritogenic mediator. J Immunol 177:2610–2620

    PubMed  CAS  Google Scholar 

  87. Monaco C, Andreakos E, Kiriakidis S et al (2004) T-cell-mediated signalling in immune, inflammatory and angiogenic processes: the cascade of events leading to inflammatory diseases. Curr Drug Targets Inflamm Allergy 3:35–42

    Article  PubMed  CAS  Google Scholar 

  88. Kasama T, Miwa Y, Isozaki T et al (2005) Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy 4:273–279

    Article  PubMed  CAS  Google Scholar 

  89. Nakahara H, Song J, Sugimoto M et al (2003) Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthritis Rheum 48:1521–1529

    Article  PubMed  CAS  Google Scholar 

  90. Winn RK, Harlan JM (2005) The role of endothelial cell apoptosis in inflammatory and immune diseases. J Thromb Haemost 3:1815–1824

    Article  PubMed  CAS  Google Scholar 

  91. Kang RY, Freire-Moar J, Sigal E et al (1996) Expression of cyclooxygenase-2 in human and an animal model of rheumatoid arthritis. Br J Rheumatol 35:711–718

    Article  PubMed  CAS  Google Scholar 

  92. Martel-Pelletier J, Pelletier JP, Fahmi H (2003) Cyclooxygenase-2 and prostaglandins in articular tissues. Semin Arthritis Rheum 33:155–167

    Article  PubMed  CAS  Google Scholar 

  93. Gately S (2000) The contributions of cyclooxygenase-2 to tumor angiogenesis. Cancer Metastasis Rev 19:19–27

    Article  PubMed  CAS  Google Scholar 

  94. Woods JM, Mogollon A, Amin MA et al (2003) The role of COX-2 in angiogenesis and rheumatoid arthritis. Exp Mol Pathol 74:282–290

    Article  PubMed  CAS  Google Scholar 

  95. Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60

    Article  PubMed  CAS  Google Scholar 

  96. Scott BB, Zaratin PF, Colombo A et al (2002) Constitutive expression of angiopoietin-1 and -2 and modulation of their expression by inflammatory cytokines in rheumatoid arthritis synovial fibroblasts. J Rheumatol 29:230–239

    PubMed  CAS  Google Scholar 

  97. Fiedler U, Augustin HG (2006) Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol 27:552–558

    Article  PubMed  CAS  Google Scholar 

  98. Harada M, Mitsuyama K, Yoshida H et al (1998) Vascular endothelial growth factor in patients with rheumatoid arthritis. Scand J Rheumatol 27:377–380

    Article  PubMed  CAS  Google Scholar 

  99. Lee SS, Joo YS, Kim WU et al (2001) Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol 19:321–324

    PubMed  CAS  Google Scholar 

  100. Paleolog EM, Young S, Stark AC et al (1998) Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis. Arthritis Rheum 41:1258–1265

    Article  PubMed  CAS  Google Scholar 

  101. Ryu S, Lee JH, Kim SI (2006) IL-17 increased the production of vascular endothelial growth factor in rheumatoid arthritis synoviocytes. Clin Rheumatol 25:16–20

    Article  PubMed  CAS  Google Scholar 

  102. Cho ML, Jung YO, Moon YM et al (2006) Interleukin-18 induces the production of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts via AP-1-dependent pathways. Immunol Lett 103:159–166

    Article  PubMed  CAS  Google Scholar 

  103. Ikeda M, Hosoda Y, Hirose S et al (2000) Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis. J Pathol 191:426–433

    Article  PubMed  CAS  Google Scholar 

  104. Malemud CJ (2007) Growth hormone, VEGF and FGF: involvement in rheumatoid arthritis. Clin Chim Acta 375:10–19

    Article  PubMed  CAS  Google Scholar 

  105. Martel-Pelletier J, Welsch DJ, Pelletier JP (2001) Metalloproteases and inhibitors in arthritic diseases. Best Pract Res Clin Rheumatol 15:805–829

    Article  PubMed  CAS  Google Scholar 

  106. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543

    Article  PubMed  CAS  Google Scholar 

  107. Lo V, Meadows SE, Saseen J (2006) When should COX-2 selective NSAIDs be used for osteoarthritis and rheumatoid arthritis? J Fam Pract 55:260–262

    PubMed  Google Scholar 

  108. Weaver AL (2003) Differentiating the new rheumatoid arthritis biologic therapies. J Clin Rheumatol 9:99–114

    Article  PubMed  Google Scholar 

  109. Moreland LW (2004) Biologic therapies on the horizon for rheumatoid arthritis. J Clin Rheumatol 10:S32–S39

    Article  PubMed  Google Scholar 

  110. McInnes IB, Liew FY (2005) Cytokine networks – towards new therapies for rheumatoid arthritis. Nat Clin Pract Rheumatol 1:31–39

    Article  PubMed  CAS  Google Scholar 

  111. Koenders MI, Joosten LA, van den Berg WB (2006) Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumour necrosis factor and IL-1 in experimental arthritis. Ann Rheum Dis 65(Suppl 3):iii29–iii33

    Article  PubMed  CAS  Google Scholar 

  112. Smolen JS, Maini RN (2006) Interleukin-6: a new therapeutic target. Arthritis Res Ther 8(Suppl 2):S5

    Article  PubMed  CAS  Google Scholar 

  113. Taylor P, Patel S, Paleolog E et al (1998) Reduced synovial vascularity following TNFα blockade in RA. Arthritis Rheum 41(Suppl 1):S295

    Google Scholar 

  114. Tas SW, Remans PH, Reedquist KA et al (2005) Signal transduction pathways and transcription factors as therapeutic targets in inflammatory disease: towards innovative antirheumatic therapy. Curr Pharm Des 11:581–611

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  116. de Bandt M, Grossin M, Weber AJ et al (2000) Suppression of arthritis and protection from bone destruction by treatment with TNP-470/AGM-1470 in a transgenic mouse model of rheumatoid arthritis. Arthritis Rheum 43:2056–2063

    Article  PubMed  Google Scholar 

  117. Arsenault AL, Lhotak S, Hunter WL et al (1998) Taxol involution of collagen-induced arthritis: ultrastructural correlation with the inhibition of synovitis and neovascularization. Clin Immunol Immunopathol 86:280–289

    Article  PubMed  CAS  Google Scholar 

  118. Oliver SJ, Cheng TP, Banquerigo ML et al (1998) The effect of thalidomide and 2 analogs on collagen induced arthritis. J Rheumatol 25:964–969

    PubMed  CAS  Google Scholar 

  119. Koch AE (2003) Angiogenesis as a target in rheumatoid arthritis. Ann Rheum Dis 62(Suppl 2):ii60–ii67

    PubMed  CAS  Google Scholar 

  120. Miotla J, Maciewicz R, Kendrew J et al (2000) Treatment with soluble VEGF receptor reduces disease severity in murine collagen-induced arthritis. Lab Invest 80:1195–1205

    Article  PubMed  CAS  Google Scholar 

  121. Lu J, Kasama T, Kobayashi K et al (2000) Vascular endothelial growth factor expression and regulation of murine collagen-induced arthritis. J Immunol 164:5922–5927

    PubMed  CAS  Google Scholar 

  122. Sone H, Kawakami Y, Sakauchi M et al (2001) Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice. Biochem Biophys Res Commun 281:562–568

    Article  PubMed  CAS  Google Scholar 

  123. Murakami M, Iwai S, Hiratsuka S et al (2006) Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocytes/macrophages. Blood 108:1849–1856

    Article  PubMed  CAS  Google Scholar 

  124. Koch AE (2000) The role of angiogenesis in rheumatoid arthritis: recent developments. Ann Rheum Dis 59(Suppl 1):i65–i71

    Article  PubMed  Google Scholar 

  125. Park YW, Kang YM, Butterfield J et al (2004) Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in rheumatoid arthritis. Am J Pathol 165:2087–2098

    PubMed  CAS  Google Scholar 

  126. Storgard CM, Stupack DG, Jonczyk A et al (1999) Decreased angiogenesis and arthritic disease in rabbits treated with an alphavbeta3 antagonist. J Clin Invest 103:47–54

    PubMed  CAS  Google Scholar 

  127. Wilder RL (2002) Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases. Ann Rheum Dis 61(Suppl 2):ii96–ii99

    PubMed  CAS  Google Scholar 

  128. Miller WH, Keenan RM, Willette RN (2000) Identification and in vivo efficacy of small-molecule antagonists of integrin alphavbeta3 (the vitronectin receptor). Drug Discov Today 5:397–408

    Article  PubMed  CAS  Google Scholar 

  129. Afuwape AO, Feldmann M, Paleolog EM (2003) Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) abrogates disease activity in murine collagen-induced arthritis. Gene Ther 10:1950–1960

    Article  PubMed  CAS  Google Scholar 

  130. Creamer P, Hochberg MC (1997) Osteoarthritis. Lancet 350:503–508

    Article  PubMed  CAS  Google Scholar 

  131. Smith MD, Triantafillou S, Parker A et al (1997) Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol 24:365–371

    PubMed  CAS  Google Scholar 

  132. Benito MJ, Veale DJ, FitzGerald O et al (2005) Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 64:1263–1267

    Article  PubMed  CAS  Google Scholar 

  133. Myers SL, Brandt KD, Ehlich JW et al (1990) Synovial inflammation in patients with early osteoarthritis of the knee. J Rheumatol 17:1662–1669

    PubMed  CAS  Google Scholar 

  134. Brooks P (2003) Inflammation as an important feature of osteoarthritis. Bull World Health Organ 81:689–690

    PubMed  Google Scholar 

  135. Spector TD, Hart DJ, Nandra D et al (1997) Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 40:723–727

    Article  PubMed  CAS  Google Scholar 

  136. Conrozier T, Chappuis-Cellier C, Richard M et al (1998) Increased serum C-reactive protein levels by immunonephelometry in patients with rapidly destructive hip osteoarthritis. Rev Rheum Engl Ed 65:759–765

    CAS  Google Scholar 

  137. Honorati MC, Neri S, Cattini L, Facchini A (2006) Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts. Osteoarthritis Cartil 14:345–352

    Article  CAS  Google Scholar 

  138. Sandy JD (2003) Proteolytic degradation of normal and osteoarthritic cartilage matrix. In: Brandt KD, Doherty M, Lohmander LS (eds) Osteoarthritis. Oxford University Press, New York, pp 82–91

    Google Scholar 

  139. Raisz LG (1999) Prostaglandins and bone: physiology and pathophysiology. Osteoarthritis Cartil 7:419–421

    Article  CAS  Google Scholar 

  140. Brune K (2004) Safety of anti-inflammatory treatment – new ways of thinking. Rheumatology (Oxford) 43(Suppl 1):i16–i20

    Article  CAS  Google Scholar 

  141. Haywood L, McWilliams DF, Pearson CI et al (2003) Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum 48:2173–2177

    Article  PubMed  CAS  Google Scholar 

  142. Haynes MK, Hume EL, Smith JB (2002) Phenotypic characterization of inflammatory cells from osteoarthritic synovium and synovial fluids. Clin Immunol 105:315–325

    Article  PubMed  CAS  Google Scholar 

  143. Ben AP, Crofford LJ, Wilder RL et al (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 372:83–87

    Article  Google Scholar 

  144. Lingen MW (2001) Role of leukocytes and endothelial cells in the development of angiogenesis in inflammation and wound healing. Arch Pathol Lab Med 125:67–71

    PubMed  CAS  Google Scholar 

  145. Giatromanolaki A, Sivridis E, Athanassou N et al (2001) The angiogenic pathway “vascular endothelial growth factor/flk-1(KDR)-receptor” in rheumatoid arthritis and osteoarthritis. J Pathol 194:101–108

    Article  PubMed  CAS  Google Scholar 

  146. Bunn HF, Poyton RO (1996) Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 76:839–885

    PubMed  CAS  Google Scholar 

  147. Jackson JR, Minton JA, Ho ML et al (1997) Expression of vascular endothelial growth factor in synovial fibroblasts is induced by hypoxia and interleukin 1beta. J Rheumatol 24:1253–1259

    PubMed  CAS  Google Scholar 

  148. Steinmeyer J, Konttinen YT (2006) Oral treatment options for degenerative joint disease-presence and future. Adv Drug Deliv Rev 58:168–211

    Article  PubMed  CAS  Google Scholar 

  149. Steinmeyer J (2004) Cytokines in osteoarthritis-current status on the pharmacological intervention. Front Biosci 9:575–580

    Article  PubMed  CAS  Google Scholar 

  150. Gaya DR, Russell RK, Nimmo N et al (2006) New genes in inflammatory bowel disease: lessons for complex disease? Lancet 367:1271–1284

    Article  PubMed  CAS  Google Scholar 

  151. Okamoto R, Watanabe M (2005) Cellular and molecular mechanisms of the epithelial repair in IBD. Dig Dis Sci 50(Suppl 1):S34

    Article  PubMed  Google Scholar 

  152. Cordiali-Fei P, Trento E, D’Agosto G et al (2006) Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-α. J Autoimmune Dis 3:5

    Article  PubMed  CAS  Google Scholar 

  153. Kapsoritakis A, Sfiridaki A, Maltezos E et al (2003) Vascular endothelial growth factor in inflammatory bowel disease. Int J Colorectal Dis 18:418–422

    Article  PubMed  Google Scholar 

  154. Girardin SE, Hugot JP, Sansonetti PJ (2003) Lessons from Nod2 studies: towards a link between Crohn’s disease and bacterial sensing. Trends Immunol 24:652–658

    Article  PubMed  CAS  Google Scholar 

  155. Ina K, Itoh J, Fukushima K et al (1999) Resistance of Crohn’s disease T cells to multiple apoptotic signals is associated with a bcl-2/Bax mucosal imbalance. J Immunol 163:1081–1090

    PubMed  CAS  Google Scholar 

  156. Pizarro TT, Michie MH, Bentz M et al (1999) IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn’s disease: expression and localization in intestinal mucosal cells. J Immunol 162:6829–6835

    PubMed  CAS  Google Scholar 

  157. Pallone F, Monteleone G (2001) Mechanisms of tissue damage in inflammatory bowel disease. Curr Opin Gastroenterol 17:307–312

    Article  PubMed  CAS  Google Scholar 

  158. Bonen DK, Ogura Y, Nicolae DL et al (2003) Crohn’s disease-associated NOD2 variants share a signaling defect in response to peptidoglycan. Gastroenterology 124:140–146

    Article  PubMed  CAS  Google Scholar 

  159. Majno G (1998) Chronic inflammation-links with angiogenesis and wound healing. Am J Pathol 153:1035–1039

    PubMed  CAS  Google Scholar 

  160. Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9:653–660

    Article  PubMed  CAS  Google Scholar 

  161. Hatoum OA, Binion DG (2005) The vasculature and inflammatory bowel disease: contribution to pathogenesis and clinical pathology. Inflamm Bowel Dis 11:304–313

    Article  PubMed  Google Scholar 

  162. Saito S, Tsuno NH, Sunami E et al (2003) Expression of platelet-derived endothelial cell growth factor in inflammatory bowel disease. J Gastroenterol 38:229–237

    Article  PubMed  CAS  Google Scholar 

  163. Hatoum OA, Binion DG, Otterson MF, Gutterman DD (2003) Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation. Gastroenterology 125:58–69

    Article  PubMed  CAS  Google Scholar 

  164. Steinhart AH, Ewe K, Griffiths AM et al (2003) Corticosteroids for maintenance of remission in Crohns disease. Cochrane Database Syst Rev 4:CD000301

    PubMed  Google Scholar 

  165. Dubinsky MC (2004) Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy and safety. Clin Gastroenterol Hepatol 2:731–743

    Article  PubMed  CAS  Google Scholar 

  166. Alfadhli AA, McDonald JW, Feagan BG (2005) Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev 4:CD003459

    Google Scholar 

  167. Lowenberg M, Peppelenbosch M, Hommes D (2006) Biological therapy in the management of recent-onset Crohn’s disease: why, when and how? Drugs 66:1431–1439

    Article  PubMed  CAS  Google Scholar 

  168. Ginsburg PM, Dassopoulos T, Ehrenpreis ED (2001) Thalidomide treatment for refractory Crohn’s disease: a review of the history, pharmacological mechanisms and clinical literature. Ann Med 33:516–525

    PubMed  CAS  Google Scholar 

  169. Ghosh S, Chaudhary R, Carpani M et al (2006) Interfering with interferons in inflammatory bowel disease. Gut 55:1071–1073

    Article  PubMed  CAS  Google Scholar 

  170. Feagan BG, Greenberg GR, Wild G et al (2005) Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med 352:2499–2507

    Article  PubMed  CAS  Google Scholar 

  171. Danese S, Semeraro S, Armuzzi A et al (2006) Biological therapies for inflammatory bowel disease: research drives clinics. Mini Rev Med Chem 6:771–784

    Article  PubMed  CAS  Google Scholar 

  172. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  PubMed  CAS  Google Scholar 

  173. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed  CAS  Google Scholar 

  174. Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7:211–217

    Article  PubMed  CAS  Google Scholar 

  175. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545

    Article  PubMed  CAS  Google Scholar 

  176. Christen S, Hagen TM, Shigenaga MK et al (1999) Microbes and malignancy: infection as a cause of human cancers. Oxford University Press, Oxford, p 35

  177. Karin M, Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749–759

    Article  PubMed  CAS  Google Scholar 

  178. de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6:24–37

    Article  PubMed  CAS  Google Scholar 

  179. Dannenberg AJ, Subbaramaiah K (2003) Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell 4:431–436

    Article  PubMed  CAS  Google Scholar 

  180. Clevers H (2004) At the crossroads of inflammation and cancer. Cell 118:671–674

    Article  PubMed  CAS  Google Scholar 

  181. Sica A, Schioppa T, Mantovani A et al (2006) Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer 42:717–727

    Article  PubMed  CAS  Google Scholar 

  182. Yoshimura A (2006) Signal transduction of inflammatory cytokines and tumor development. Cancer Sci 97:439–447

    Article  PubMed  CAS  Google Scholar 

  183. Saijo Y, Tanaka M, Miki M et al (2002) Proinflammatory cytokine IL-1β promotes tumor growth of lewis lung carcinoma by induction of angiogenic factors: in vivo analysis of tumor-stromal interaction. J Immunol 169:469–475

    PubMed  CAS  Google Scholar 

  184. Balkwill F (2006) TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev 25:409–416

    Article  PubMed  CAS  Google Scholar 

  185. Coussens LM, Tinkle CL, Hanahan DH et al (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103:481–490

    Article  PubMed  CAS  Google Scholar 

  186. Esposito I, Menicagli M, Funel N et al (2004) Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J Clin Pathol 57:630–636

    Article  PubMed  CAS  Google Scholar 

  187. Tsujii M, Kawano S, Tsuji S et al (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716

    Article  PubMed  CAS  Google Scholar 

  188. Ferrara N (2002) VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2:795–803

    Article  PubMed  CAS  Google Scholar 

  189. Ferrara N, Alitalo K (1999) Clinical applications of angiogenic growth factors and their inhibitors. Nat Med 5:359–364

    Article  Google Scholar 

  190. Sang QX, Jin Y, Newcomer RG et al (2006) Matrix metalloproteinase inhibitors as prospective agents for the prevention and treatment of cardiovascular and neoplastic diseases. Curr Top Med Chem 6:289–316

    Article  PubMed  CAS  Google Scholar 

  191. Wadler S (2007) Targeted therapy in colorectal cancer. Clin Colorectal Cancer 6:357–361

    Article  PubMed  CAS  Google Scholar 

  192. Flis S, Soltysiak-Pawluczuk D, Jedrych A et al (2006) Antiangiogenic effect of sulindac sulfide could be secondary to induction of apoptosis and cell cycle arrest. Anticancer Res 26:3033–3041

    PubMed  CAS  Google Scholar 

  193. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444:860–867

    Article  PubMed  CAS  Google Scholar 

  194. Kerner A, Avizohar O, Sella R et al (2005) Association between elevated liver enzymes and c-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arterioscler Thromb Vasc Biol 25:193–197

    PubMed  CAS  Google Scholar 

  195. Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874

    Article  PubMed  CAS  Google Scholar 

  196. Goudriaan JR, Tacken PJ, Dahlmans VE et al (2001) Protection from obesity in mice lacking the VLDL receptor. Arterioscler Thromb Vasc Biol 21:1488–1493

    PubMed  CAS  Google Scholar 

  197. Mikhailenko I, Krylov D, Argraves KM et al (1997) Cellular internalization and degradation of thrombospondin-1 is mediated by the amino-terminal heparin binding domain (HBD). High affinity interaction of dimeric HBD with the low density lipoprotein receptor-related protein. J Biol Chem 272:6784–6791

    Article  PubMed  CAS  Google Scholar 

  198. Argraves KM, Battey FD, MacCalman CD et al (1995) The very low density lipoprotein receptor mediates the cellular catabolism of lipoprotein lipase and urokinase-plasminogen activator inhibitor type I complexes. J Biol Chem 270:26550

    Article  PubMed  CAS  Google Scholar 

  199. Kasza A, Petersen HH, Heegaard CW et al (1997) Specifity of serine proteinase/serpin complex binding to very-low-density lipoprotein receptor and α2-macroglobulin receptor/low-density-lipoprotein-receptor-related protein. Eur J Biochem 248:270–281

    Article  PubMed  CAS  Google Scholar 

  200. Hembrough TA, Ruiz JF, Swerdlow BM et al (2004) Identification and characterization of a very low density lipoprotein receptor-binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity. Blood 103:3374–3380

    Article  PubMed  CAS  Google Scholar 

  201. Vettor R, Milan G, Rossato M et al (2005) Review article: adipocytokines and insulin resistance. Aliment Pharmacol Ther 22(Suppl 2):3–10

    Article  PubMed  CAS  Google Scholar 

  202. Monteiro R, de Castro PM, Calhau C et al (2006) Adipocyte size and liability to cell death. Obes Surg 16:804–806

    Article  PubMed  Google Scholar 

  203. Cinti S, Mitchell G, Barbatelli G et al (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355

    Article  PubMed  CAS  Google Scholar 

  204. Rupnick MA, Panigrahy D, Zhang CY et al (2002) Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci USA 99:10730–10735

    Article  PubMed  CAS  Google Scholar 

  205. Rose DP, Komninou D, Stephenson GD (2004) Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev 5:153–165

    Article  PubMed  CAS  Google Scholar 

  206. Fukumura D, Ushiyama A, Duda DG et al (2003) Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis. Circ Res 93:88–97

    Article  CAS  Google Scholar 

  207. Leonhardt M, Hrupka B, Langhans W (1999) New approaches in the pharmacological treatment of obesity. Eur J Nutr 38:1–13

    Article  PubMed  CAS  Google Scholar 

  208. Bray GA (1999) Overweight is risking fate. J Clin Endocrinol Metab 84:10–12

    Article  CAS  Google Scholar 

  209. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W (2004) Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10:625–632

    Article  PubMed  CAS  Google Scholar 

  210. Simons M (2005) Angiogenesis, arteriogenesis, and diabetes paradigm reassessed? J Am Coll Cardiol 46:835–837

    Article  PubMed  Google Scholar 

  211. Waltenberger J, Lange J, Kranz A (2000) Vascular endothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus. A potential predictor for the individual capacity to develop collaterals. Circulation 102:185–190

    PubMed  CAS  Google Scholar 

  212. Adamis AP, Aiello LP, D’Amato RA (1999) Angiogenesis and ophthalmic disease. Angiogenesis 3:9–14

    Article  PubMed  CAS  Google Scholar 

  213. Duraisamy Y, Slevin M, Smith N et al (2001) Effect of glycation on basic fibroblast growth factor induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: possible relevance to wound healing in diabetes. Angiogenesis 4:277–288

    Article  PubMed  CAS  Google Scholar 

  214. Schmidt AM, Yan SD, Wautier J-L et al (1999) Activation of Receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 84:489–497

    PubMed  CAS  Google Scholar 

  215. Lebovitz HE (2006) Therapeutic options in development for management of diabetes: pharmacologic agents and new technologies. Endocr Pract 12(Suppl 1):142–147

    PubMed  Google Scholar 

  216. Pandya NM, Dhalla NS, Santani DD (2006) Angiogenesis – a new target for future therapy. Vascul Pharmacol 44:265–274

    Article  PubMed  CAS  Google Scholar 

  217. Steed DL (2006) Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity ulcers. Plast Reconstr Surg 117(7 Suppl):143S–149S

    Article  PubMed  CAS  Google Scholar 

  218. Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  PubMed  CAS  Google Scholar 

  219. Hansson G (2005) Inflammation, atherosclerosis, and coronary artery disease. New Engl J Med 352:1685–1695

    Article  PubMed  CAS  Google Scholar 

  220. Weber C (2005) Platelets and chemokines in atherosclerosis: partners in crime. Circ Res 96:612–616

    Article  PubMed  CAS  Google Scholar 

  221. Moulton KS, Heller E, Konerding MA et al (1999) Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99:1726–1732

    PubMed  CAS  Google Scholar 

  222. Bresalier RS, SandlerRS, Quan H et al (2005) Adenomatous polyp prevention on Vioxx (approve) trial investigators. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. New Engl J Med 352:1092–1102

    Article  PubMed  CAS  Google Scholar 

  223. Crisby M, Nordin-Fredriksson G, Shah PK et al (2001) Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques. Implications for plaque stabilization. Circulation 103:926–933

    PubMed  CAS  Google Scholar 

  224. Veillard NR, Braunersreuther V, Arnaud C et al (2006) Simvastatin modulates chemokine and chemokine receptor expression by geranylgeranyl isoprenoid pathway in human endothelial cells and macrophages. Atherosclerosis 188:51–58

    Article  PubMed  CAS  Google Scholar 

  225. Clarke MC, Figg N, Maguire J et al (2006) Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med 12:1075–1080

    Article  PubMed  CAS  Google Scholar 

  226. Schaub FJ, Han DK, Liles WC et al (2000) Fas/FADD-mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells. Nat Med 6:790–796

    Article  PubMed  CAS  Google Scholar 

  227. Folkman J (2001) Angiogenesis. In: Jameson JL, Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL (eds) Harrison’s principles of internal medicine, 15th edn. McGraw-Hill, USA

    Google Scholar 

  228. Zhang SX, Ma JX (2007) Ocular neovascularization: implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res 26:1–37

    Article  PubMed  CAS  Google Scholar 

  229. Sakurai E, Anand A, Ambati BK et al (2003) Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44:3578–3585

    Article  PubMed  Google Scholar 

  230. Bora P, Sohn J, Cruz J et al (2005) Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization. J Immunol 174:491–497

    PubMed  CAS  Google Scholar 

  231. Mitamura Y, Takeuchi S, Matsuda A et al (2001) Monocyte chemotactic protein-1 in the vitreous of patients with proliferative diabetic retinopathy. Ophthalmologica 215:415–418

    Article  PubMed  CAS  Google Scholar 

  232. Chang TS, Tonnu IQ, Globe DR et al (2004) Longitudinal changes in self-reported visual functioning in AMD patients in a randomized controlled phase I/II trial of Lucentis™ (ranibizumab; rHuFABv2). Invest Ophthalmol Vis Sci 45:E3098

    Article  Google Scholar 

  233. Eugene WM, Adamis AP (2005) Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneratio. Can J Ophthalmol 40:352–368

    Google Scholar 

  234. Steinbrook R (2006) The price of sight-ranibizumab, bevacizumab, and the treatment of macular degeneration. N Engl J Med 355:1409–1412

    Article  PubMed  CAS  Google Scholar 

  235. Ciulla TA, Criswell MH, Danis RP et al (2001) Intravitreal triamcinolone acetonide inhibits choroidal neovascularization in a laser-treated rat model. Arch Ophthalmol 119:399–404

    PubMed  CAS  Google Scholar 

  236. Markomichelakis NN, Theodossiadis PG, Sfikakis PP (2005) Regression of neovascular age-related macular degeneration following infliximab therapy. Am J Ophthalmol 139:537–540

    Article  PubMed  Google Scholar 

  237. Soares R, Azevedo I (2007) Inhibition of S1P by polyphenols prevents inflammation and angiogenesis: NFkappaB, a downstream effector? Free Radic Biol Med 42:311

    Article  PubMed  CAS  Google Scholar 

  238. Soares R, Azevedo I (2006) Apigenin: is it a pro- or anti-inflammatory agent? Am J Pathol 168:1762–1763

    Article  PubMed  Google Scholar 

  239. Monteiro R, Guerreiro S, Soares R et al (2006) FASEB J Suppl: A568

  240. Incio J, Lopes R, Azevedo I et al (2006) Prevention of both angio and atherogenesis: inhibitory properties of polyphenols (Xanthumol) in smooth muscle cells. Eur J Med Res 11(Suppl II):122

    Google Scholar 

Download references

Acknowledgments

The authors would like to thank Professor Isabel Azevedo for her helpful discussions, comments and revision of the manuscript. Carla Costa was funded by “Fundação da Ciência e Tecnologia” (SFRH/BPD/20832/2004).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Raquel Soares.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Costa, C., Incio, J. & Soares, R. Angiogenesis and chronic inflammation: cause or consequence?. Angiogenesis 10, 149–166 (2007). https://doi.org/10.1007/s10456-007-9074-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10456-007-9074-0

Keywords

Navigation