Skip to main content

Role of Angiogenesis in the Pathogenesis of Arthritis: Potential Therapeutic Applications

  • Chapter
  • First Online:
Therapeutic Angiogenesis for Vascular Diseases

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, associated with inflammation of the synovial lining of tendons and joints. Despite major advances in the treatment of RA, using biological therapies, particularly treatments targeted at cytokines such as tumour necrosis factor α (TNFα), there is still a significant unmet need in RA, due to non-responders and increased infections following TNFα blockade. Dysregulated angiogenesis contributes to diseases associated with excessive vascularisation, such as cancer and certain forms of ocular disease, and has recently been linked to RA. A number of pro- and anti-angiogenic factors are expressed in RA synovium, including vascular endothelial cell growth factor (VEGF). As is the case in cancer, hypoxia is a feature of RA, and the hypoxia/Hypoxia inhibitors factor (HIF) pathway and HIF target genes, particularly VEGF, contribute to RA severity. Therefore, angiogenesis and HIF inhibitors that are already in use against cancer could also be potential candidates for the treatment of RA. In RA, therapies aimed at inhibiting angiogenesis, such as inhibitors of VEGF, have shown efficacy in animal models of arthritis. It is therefore possible that in the future, treatments such as bevacizumab may prove to be beneficial in RA in combination with existing modalities such as TNFα inhibition.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover 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

References

  • Afuwape A, Kiriakidis S, et al. (2002) The role of the angiogenic molecule VEGF in the pathogenesis of rheumatoid arthritis. Histol Histopathol 17:961–972.

    PubMed  CAS  Google Scholar 

  • Afuwape AO, Feldmann M, et al. (2003) Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) abrogates disease activity in murine collagen-induced arthritis. Gene Ther 10(23):1950–1960.

    PubMed  CAS  Google Scholar 

  • Aggarwal A, Panda S, et al. (2004) Effect of etanercept on matrix metalloproteinases and angiogenic vascular endothelial growth factor: A time kinetic study. Ann Rheum Dis 63(7):891–892.

    PubMed  CAS  Google Scholar 

  • Akhavani MA, Madden L, et al. (2009) Hypoxia upregulates angiogenesis and synovial cell migration in rheumatoid arthritis. Arthritis Res Ther 11(3):R64.

    PubMed  Google Scholar 

  • Arsenault AL, Lhotak S, et al. (1998) Taxol involution of collagen-induced arthritis: ultrastructural correlation with the inhibition of synovitis and neovascularization. Clin Immunol Immunopathol 86(3):280–289.

    PubMed  CAS  Google Scholar 

  • Asahara T, Takahashi T, et al. (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. Embo J 18(14):3964–3972.

    PubMed  CAS  Google Scholar 

  • Autiero M, Waltenberger J, et al. (2003) Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med 9(7):936–943.

    PubMed  CAS  Google Scholar 

  • Bainbridge J, Madden L, et al. (2007) Methionine aminopeptidase-2 blockade reduces chronic collagen-induced arthritis: Potential role for angiogenesis inhibition. Arthritis Research and Therapy 9(6):R127.

    PubMed  Google Scholar 

  • Bainbridge J, Sivakumar B, et al. (2006) Angiogenesis as a therapeutic target in arthritis: Lessons from oncology. Curr Pharm Des 12(21):2631–2644.

    PubMed  CAS  Google Scholar 

  • Ballara SC, Taylor PC, et al. (2001) Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum 44(9):2055–2064.

    PubMed  CAS  Google Scholar 

  • Barrett EM, Scott DG, et al. (2000) The impact of rheumatoid arthritis on employment status in the early years of disease: A UK community-based study. Rheumatology (Oxford) 39(12):1403–1409.

    CAS  Google Scholar 

  • Bernier SG, Lazarus DD, et al. (2004) A methionine aminopeptidase-2 inhibitor, PPI-2458, for the treatment of rheumatoid arthritis. Proc Natl Acad Sci USA 101(29):10768–10773.

    PubMed  CAS  Google Scholar 

  • Berse B, Hunt JA, et al. (1999) Hypoxia augments cytokine (transforming growth factor-beta (TGF-beta) and IL-1)-induced vascular endothelial growth factor secretion by human synovial fibroblasts. Clin Exp Immunol 115(1):176–182.

    PubMed  CAS  Google Scholar 

  • Blake DR, Merry P, et al. (1989) Hypoxic-reperfusion injury in the inflamed human joint. Lancet 1(8633):289–293.

    PubMed  CAS  Google Scholar 

  • Block KM, Hui W, et al.(2009) Direct Inhibition of Hypoxia-Inducible Transcription Factor Complex with Designed Dimeric Epidithiodiketopiperazine. J Am Chem Soc (DOI: 10.1021/ja807601b, June 17, 2009).

    Google Scholar 

  • Bongartz T, Sutton AJ, et al. (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: Systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295(19):2275–2285.

    PubMed  CAS  Google Scholar 

  • Bongartz T, Warren FC, et al. (2009) Etanercept therapy in rheumatoid arthritis and the risk of malignancies: A systematic review and individual patient data meta-analysis of randomised controlled trials. Ann Rheum Dis 68(7):1177–1183.

    PubMed  CAS  Google Scholar 

  • Bottomley MJ, Webb NJ, et al. (2000) Placenta growth factor (PlGF) induces vascular endothelial growth factor (VEGF) secretion from mononuclear cells and is co-expressed with VEGF in synovial fluid. Clin Exp Immunol 119(1):182–188.

    PubMed  CAS  Google Scholar 

  • Bottomley MJ, Webb NJ, et al. (1999) Peripheral blood mononuclear cells from patients with rheumatoid arthritis spontaneously secrete vascular endothelial growth factor (VEGF): Specific up-regulation by tumour necrosis factor-alpha (TNF-alpha) in synovial fluid. Clin Exp Immunol 117(1):171–176.

    PubMed  CAS  Google Scholar 

  • Brahn E, Banquerigo ML, et al. (2008) An angiogenesis inhibitor, 2-methoxyestradiol, involutes rat collagen-induced arthritis and suppresses gene expression of synovial vascular endothelial growth factor and basic fibroblast growth factor. J Rheumatol 35(11):2119–2128.

    PubMed  CAS  Google Scholar 

  • Brown RA, Weiss JB, et al. (1980) Angiogenic factor from synovial fluid resembling that from tumours. Lancet 1(8170):682–685.

    PubMed  CAS  Google Scholar 

  • Bruce TO (2008) Comorbid depression in rheumatoid arthritis: Pathophysiology and clinical implications. Curr Psychiatry Rep 10(3):258–264.

    PubMed  Google Scholar 

  • Bruyn GA, Tate G, et al. (2008) Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: A 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study. Ann Rheum Dis 67(8):1090–1095.

    PubMed  CAS  Google Scholar 

  • Carmeliet P, Ferreira V, et al. (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573):435–439.

    PubMed  CAS  Google Scholar 

  • Ceponis A, Konttinen YT, et al. (1998) Synovial lining, endothelial and inflammatory mononuclear cell proliferation in synovial membranes in psoriatic and reactive arthritis: A comparative quantitative morphometric study. Br J Rheumatol 37(2):170–178.

    PubMed  CAS  Google Scholar 

  • Clavel G, Bessis N, et al. (2007) Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction. Clin Immunol 124(2):158–164.

    PubMed  CAS  Google Scholar 

  • Cook KM, Hilton ST, et al. (2009) Epidithiodiketopiperazines block the interaction between hypoxia inducible factor-1alpha (HIF-1alpha) and p300 by a zinc ejection mechanism. J Biol Chem 284:26831–26838

    PubMed  CAS  Google Scholar 

  • Cramer T, Yamanishi Y, et al. (2003) HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112(5):645–657.

    PubMed  CAS  Google Scholar 

  • Cress WD, Seto E (2000) Histone deacetylases, transcriptional control, and cancer. J Cell Physiol 184(1):1–16.

    PubMed  CAS  Google Scholar 

  • Curran MP, McKeage K (2009) Bortezomib: A review of its use in patients with multiple myeloma. Drugs 69(7):859–888.

    PubMed  CAS  Google Scholar 

  • de Bandt M, Ben Mahdi MH, et al. (2003) Blockade of vascular endothelial growth factor receptor I (VEGF-RI), but not VEGF-RII, suppresses joint destruction in the K/BxN model of rheumatoid arthritis. J Immunol 171(9):4853–4859.

    PubMed  Google Scholar 

  • de Bandt M, Grossin M, 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(9):2056–2063.

    PubMed  Google Scholar 

  • DeBusk LM, Chen Y, et al. (2003) Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis. Arthritis Rheum 48(9):2461–2471.

    PubMed  CAS  Google Scholar 

  • Del Rincon I, O’Leary DH, et al. (2007) Acceleration of atherosclerosis during the course of rheumatoid arthritis. Atherosclerosis195:354–360.

    Google Scholar 

  • Del Rincon I, Williams K, et al. (2003) Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 48(7):1833–1840.

    Google Scholar 

  • Edwards JC, Szczepanski L, et al. (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350(25):2572–2581.

    PubMed  CAS  Google Scholar 

  • Eklund KK, Joensuu H (2003) Treatment of rheumatoid arthritis with imatinib mesylate: clinical improvement in three refractory cases. Ann Med 35(5):362–367.

    PubMed  CAS  Google Scholar 

  • Eklund KK, Lindstedt K, et al. (2008) Maintained efficacy of the tyrosine kinase inhibitor imatinib mesylate in a patient with rheumatoid arthritis. J Clin Rheumatol 14(5):294–296.

    PubMed  Google Scholar 

  • Ema M, Hirota K, et al. (1999) Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: Their stabilization and redox signal-induced interaction with CBP/p300. EMBO J 18(7):1905–1914.

    PubMed  CAS  Google Scholar 

  • Ertel AN, Millender LH, et al. (1988) Flexor tendon ruptures in patients with rheumatoid arthritis. J Hand Surg [Am] 13(6):860–866.

    CAS  Google Scholar 

  • Etherington PJ, Winlove P, et al. (2002) VEGF release is associated with reduced oxygen tensions in experimental inflammatory arthritis. Clin Exp Rheumatol 20(6):799–805.

    PubMed  CAS  Google Scholar 

  • Fava RA, Olsen N J, et al. (1994) Vascular permeability factor/endothelial growth factor (VPF/VEGF): Accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med 180(1):341–346.

    PubMed  CAS  Google Scholar 

  • Fearon U, Griosios K, et al. (2003) Angiopoietins, growth factors, and vascular morphology in early arthritis. J Rheumatol 30(2):260–268.

    PubMed  CAS  Google Scholar 

  • Firestein GS (2005) Pathogenesis of rheumatoid arthritis: How early is early? Arthritis Res Ther 7(4):157–159.

    PubMed  Google Scholar 

  • Folkman J (1971) Tumor angiogenesis: Therapeutic implications. N Engl J Med 285(21):1182–1186.

    PubMed  CAS  Google Scholar 

  • Furst DE (2008) Serum Immunoglobulins and Risk of Infections with Biologic Therapies for Rheumatoid Arthritis. Semin Arthritis Rheum 39:18–29.

    PubMed  Google Scholar 

  • Gabriel SE, Crowson CS, et al. (2003) Survival in rheumatoid arthritis: A population-based analysis of trends over 40 years. Arthritis Rheum 48(1):54–58.

    PubMed  Google Scholar 

  • Genovese MC, McKay JD, et al. (2008) Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: The tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 58(10):2968–2980.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Giatromanolaki A, Sivridis E, et al. (2003) Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 5(4):R193–R201.

    PubMed  CAS  Google Scholar 

  • Goldring SR (2000) The final pathogenetic steps in focal bone erosions in rheumatoid arthritis. Ann Rheum Dis 59(Suppl 1):i72–i74.

    PubMed  Google Scholar 

  • Gonzalez-Gay MA, Gonzalez-Juanatey C, et al. (2005) Rheumatoid arthritis: A disease associated with accelerated atherogenesis. Semin Arthritis Rheum 35(1):8–17.

    PubMed  Google Scholar 

  • Gospodarowicz D, Abraham JA, et al. (1989) Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci USA 86(19):7311–7315.

    PubMed  CAS  Google Scholar 

  • Gravallese EM, Pettit AR, et al. (2003) Angiopoietin-1 is expressed in the synovium of patients with rheumatoid arthritis and is induced by tumour necrosis factor alpha. Ann Rheum Dis 62(2):100–107.

    PubMed  CAS  Google Scholar 

  • Grisar J, Aletaha D, et al. (2005) Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 111(2):204–211.

    PubMed  Google Scholar 

  • Grunstein M (1997) Histone acetylation in chromatin structure and transcription. Nature 389(6649):349–352.

    PubMed  CAS  Google Scholar 

  • Harada M, Mitsuyama K, et al. (1998) Vascular endothelial growth factor in patients with rheumatoid arthritis. Scand J Rheumatol 27(5):377–380.

    PubMed  CAS  Google Scholar 

  • Hideshima T, Mitsiades C, et al. (2003) Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 101(4):1530–1534.

    PubMed  CAS  Google Scholar 

  • Hirohata S, Yanagida T, et al. (2004) Enhanced generation of endothelial cells from CD34+ cells of the bone marrow in rheumatoid arthritis: Possible role in synovial neovascularization. Arthritis Rheum 50(12):3888–3896.

    PubMed  Google Scholar 

  • Hitchon C, Wong K, et al. (2002) Hypoxia-induced production of stromal cell-derived factor 1 (CXCL12) and vascular endothelial growth factor by synovial fibroblasts. Arthritis Rheum 46(10):2587–2597.

    PubMed  CAS  Google Scholar 

  • Hitchon CA, El-Gabalawy HS, et al. (2009) Characterization of synovial tissue from arthritis patients: A proton magnetic resonance spectroscopic investigation. Rheumatol Int

    Google Scholar 

  • Hollander AP, Corke KP, et al. (2001) Expression of hypoxia-inducible factor 1alpha by macrophages in the rheumatoid synovium: Implications for targeting of therapeutic genes to the inflamed joint. Arthritis Rheum 44(7):1540–1544.

    PubMed  CAS  Google Scholar 

  • Jackson JK, Higo T, et al. (2008) Topoisomerase inhibitors as anti-arthritic agents. Inflamm Res 57(3):126–134.

    PubMed  CAS  Google Scholar 

  • Jain A, Kiriakidis S, et al. (2006) Targeting rheumatoid tenosynovial angiogenesis with cytokine inhibitors. Clin Orthop Relat Res 446:268–277.

    PubMed  Google Scholar 

  • Jain A, Nanchahal J, et al. (2001) Production of cytokines, vascular endothelial growth factor, matrix metalloproteinases, and tissue inhibitor of metalloproteinases 1 by tenosynovium demonstrates its potential for tendon destruction in rheumatoid arthritis. Arthritis Rheum 44(8):1754–1760.

    PubMed  CAS  Google Scholar 

  • Jin P, Zhang J, et al. (2008) Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Research and Therapy 10(4):R73.

    PubMed  Google Scholar 

  • Josefsson E, Tarkowski A (1997) Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol. Arthritis Rheum 40(1):154–163.

    PubMed  CAS  Google Scholar 

  • Kaelin WG, Jr (2009) Treatment of kidney cancer: Insights provided by the VHL tumor-suppressor protein. Cancer 115(10 Suppl):2262–2272.

    PubMed  CAS  Google Scholar 

  • Kameda H, Ishigami H, et al. (2006) Imatinib mesylate inhibits proliferation of rheumatoid synovial fibroblast-like cells and phosphorylation of Gab adapter proteins activated by platelet-derived growth factor. Clin Exp Immunol 144(2):335–341.

    PubMed  CAS  Google Scholar 

  • Kaplan MJ (2006) Cardiovascular disease in rheumatoid arthritis. Curr Opin Rheumatol 18(3):289–297.

    PubMed  CAS  Google Scholar 

  • Kasama T, Kobayashi K, et al. (2000) Expression of vascular endothelial growth factor by synovial fluid neutrophils in rheumatoid arthritis (RA). Clin Exp Immunol 121(3):533–538.

    PubMed  CAS  Google Scholar 

  • Keesal N, Wasserman MJ, et al. (1999) Thalidomide in the treatment of refractory rheumatoid arthritis. J Rheumatol 26(11):2344–2347.

    PubMed  CAS  Google Scholar 

  • Khanum SA, Shashikanth S, et al. (2004) Synthesis and anti-inflammatory activity of benzophenone analogues. Bioorg Chem 32(4):211–222.

    PubMed  CAS  Google Scholar 

  • Kikuchi K, Kubo M, et al. (1998) Serum concentrations of vascular endothelial growth factor in collagen diseases. Br J Dermatol 139(6):1049–1051.

    PubMed  CAS  Google Scholar 

  • Kim JM, Ho SH, et al. (2002) Angiostatin gene transfer as an effective treatment strategy in murine collagen-induced arthritis. Arthritis Rheum 46(3):793–801.

    PubMed  CAS  Google Scholar 

  • Kim MS, Kwon HJ, et al. (2001) Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 7(4):437–443.

    PubMed  Google Scholar 

  • Koch AE, Halloran MM, et al. (1996) Hepatocyte growth factor. A cytokine mediating endothelial migration in inflammatory arthritis. Arthritis Rheum 39(9):1566–1575.

    PubMed  CAS  Google Scholar 

  • Koch AE, Harlow LA, et al. (1994) Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 152(8):4149–4156.

    PubMed  CAS  Google Scholar 

  • Kremer JM, Westhovens R, et al. (2003) Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med 349(20):1907–1915.

    PubMed  CAS  Google Scholar 

  • Kumar P, Erroi A, et al. (1985) Weibel-Palade bodies as a marker for neovascularization induced by tumor and rheumatoid angiogenesis factors. Cancer Res 45(9):4339–4348.

    PubMed  CAS  Google Scholar 

  • Kumazawa E, Hirotani K, et al. (1997) Synthesis and antitumor activity of novel benzophenone derivatives. Chem Pharm Bull (Tokyo) 45(9):1470–1474.

    CAS  Google Scholar 

  • Kung AL, Zabludoff SD, et al. (2004) Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell 6(1):33–43.

    PubMed  CAS  Google Scholar 

  • Kuryliszyn-Moskal A, Klimiuk PA, et al. (2006) A study on vascular endothelial growth factor and endothelin-1 in patients with extra-articular involvement of rheumatoid arthritis. Clin Rheumatol 25(3):314–319.

    PubMed  Google Scholar 

  • Kwon HJ, Kim MS, et al. (2002) Histone deacetylase inhibitor FK228 inhibits tumor angiogenesis. Int J Cancer 97(3):290–296.

    PubMed  CAS  Google Scholar 

  • Latour F, Zabraniecki L, et al. (2001) Does vascular endothelial growth factor in the rheumatoid synovium predict joint destruction? A clinical, radiological, and pathological study in 12 patients monitored for 10 years. Joint Bone Spine 68(6):493–498.

    PubMed  CAS  Google Scholar 

  • Lee SS, Joo YS, et al. (2001) Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol 19(3):321–324.

    PubMed  CAS  Google Scholar 

  • Lee SW, Kim JH, et al. (2008) Bortezomib attenuates murine collagen-induced arthritis. Ann Rheum Dis 68:1761–1767.

    PubMed  Google Scholar 

  • Lee YA, Kim JY, et al. (2007) Synovial proliferation differentially affects hypoxia in the joint cavities of rheumatoid arthritis and osteoarthritis patients. Clin Rheumatol 26(12):2023–2029.

    PubMed  Google Scholar 

  • Lu J, Kasama T, et al. (2000) Vascular endothelial growth factor expression and regulation of murine collagen-induced arthritis. J Immunol 164(11):5922–5927.

    PubMed  CAS  Google Scholar 

  • Lund-Olesen K (1970) Oxygen tension in synovial fluids. Arthritis Rheum 13(6):769–776.

    PubMed  CAS  Google Scholar 

  • Luttun A, Tjwa M, et al. (2002) Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 8(8):831–840.

    PubMed  CAS  Google Scholar 

  • Mabjeesh NJ, Escuin D, et al. (2003) 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3(4):363–375.

    PubMed  CAS  Google Scholar 

  • Macias I, Garcia-Perez S, et al. (2005) Modification of pro- and antiinflammatory cytokines and vascular-related molecules by tumor necrosis factor-a blockade in patients with rheumatoid arthritis. J Rheumatol 32(11):2102–2108.

    PubMed  CAS  Google Scholar 

  • Manabe H, Nasu Y, et al. (2008) Inhibition of histone deacetylase down-regulates the expression of hypoxia-induced vascular endothelial growth factor by rheumatoid synovial fibroblasts. Inflamm Res 57(1):4–10.

    PubMed  CAS  Google Scholar 

  • Maradit-Kremers H, Crowson CS, et al. (2005a). Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population-based cohort study. Arthritis Rheum 52(2):402–411.

    PubMed  Google Scholar 

  • Maradit-Kremers H, Nicola PJ, et al. (2005b). Cardiovascular death in rheumatoid arthritis: A population-based study. Arthritis Rheum 52(3):722–732.

    PubMed  Google Scholar 

  • Maxwell PH, Wiesener MS, et al. (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399(6733):271–275.

    PubMed  CAS  Google Scholar 

  • Mayerhofer M, Valent P, et al. (2002) BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1alpha, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. Blood 100(10):3767–3775.

    PubMed  CAS  Google Scholar 

  • Miotla J, Maciewicz R, et al. (2000) Treatment with soluble VEGF receptor reduces disease severity in murine collagen-induced arthritis. Lab Invest 80(8):1195–1205.

    PubMed  CAS  Google Scholar 

  • Nadareishvili Z, Michaud K, et al. (2008) Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: A nested, case-control study. Arthritis Rheum 59(8):1090–1096.

    PubMed  Google Scholar 

  • Nagashima M, Wauke K, et al. (2000) Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis. Rheumatology (Oxford) 39(11):1255–1262.

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Nakamura C, Matsushita I, et al. (2008) Anti-arthritic effects of combined treatment with histone deacetylase inhibitor and low-intensity ultrasound in the presence of microbubbles in human rheumatoid synovial cells. Rheumatology (Oxford) 47(4):418–424.

    CAS  Google Scholar 

  • Nakashima M, Eguchi K, et al. (1994) Expression of basic fibroblast growth factor in synovial tissues from patients with rheumatoid arthritis: Detection by immunohistological staining and in situ hybridisation. Ann Rheum Dis 53(1):45–50.

    PubMed  CAS  Google Scholar 

  • Naughton D, Whelan M, et al. (1993) An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy. FEBS Lett 317(1–2):135–138.

    PubMed  CAS  Google Scholar 

  • Oliver SJ, Cheng TP, et al. (1998) The effect of thalidomide and 2 analogs on collagen induced arthritis. J Rheumatol 25(5):964–996.

    PubMed  CAS  Google Scholar 

  • Olsson AK, Dimberg A, et al. (2006) VEGF receptor signalling- in control of vascular function. Nat Rev Mol Cell Biol 7(5):359–371.

    PubMed  CAS  Google Scholar 

  • Pache M, Schwarz HA, et al. (2002) Elevated plasma endothelin-1 levels and vascular dysregulation in patients with rheumatoid arthritis. Med Sci Monit 8(9):CR616–CR619.

    PubMed  CAS  Google Scholar 

  • Paleolog EM, Young S, et al. (1998) Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis. Arthritis Rheum 41(7):1258–1265.

    PubMed  CAS  Google Scholar 

  • Paniagua RT, Sharpe O, et al. (2006) Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis. J Clin Invest 116(10):2633–2642.

    PubMed  CAS  Google Scholar 

  • Peters CL, Morris CJ, et al. (2004) The transcription factors hypoxia-inducible factor 1alpha and Ets-1 colocalize in the hypoxic synovium of inflamed joints in adjuvant-induced arthritis. Arthritis Rheum 50(1):291–296.

    PubMed  CAS  Google Scholar 

  • Plum SM, Park EJ, et al. (2009) Disease modifying and antiangiogenic activity of 2-methoxyestradiol in a murine model of rheumatoid arthritis. BMC Musculoskelet Disord 10:46.

    PubMed  Google Scholar 

  • Pufe T, Petersen W, et al. (2001) Splice variants VEGF121 and VEGF165 of the angiogenic peptide vascular endothelial cell growth factor are expressed in the synovial tissue of patients with rheumatoid arthritis. J Rheumatol 28(7):1482–1485.

    PubMed  CAS  Google Scholar 

  • Rapisarda A, Uranchimeg B, et al. (2002) Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway. Cancer Res 62(15):4316–4324.

    PubMed  CAS  Google Scholar 

  • Recio-Mayoral A, Mason JC, et al. (2009) Chronic inflammation and coronary microvascular dysfunction in patients without risk factors for coronary artery disease. Eur Heart J 30(15):1837–1843.

    PubMed  CAS  Google Scholar 

  • Remmers EF, Sano H, et al. (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(1):7–13.

    PubMed  CAS  Google Scholar 

  • Rooney M, Condell D, et al. (1988) Analysis of the histologic variation of synovitis in rheumatoid arthritis. Arthritis Rheum 31(8):956–963.

    PubMed  CAS  Google Scholar 

  • Rothschild BM, Masi AT, (1982) Pathogenesis of rheumatoid arthritis: A vascular hypothesis. Semin Arthritis Rheum 12(1):11–31.

    PubMed  CAS  Google Scholar 

  • Ruger B, Giurea A, et al. (2004) Endothelial precursor cells in the synovial tissue of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum 50(7):2157–2166.

    PubMed  Google Scholar 

  • Saharinen P, Kerkela K, et al. (2005) Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2. J Cell Biol 169(2):239–243.

    PubMed  CAS  Google Scholar 

  • Sandler C, Joutsiniemi S, et al. (2006) Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts. Biochem Biophys Res Commun 347(1):31–35.

    PubMed  CAS  Google Scholar 

  • Sano H, Engleka K, et al. (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(2):553–565.

    PubMed  CAS  Google Scholar 

  • Sano H, Forough R, et al. (1990) Detection of high levels of heparin binding growth factor-1 (acidic fibroblast growth factor) in inflammatory arthritic joints. J Cell Biol 110(4):1417–1426.

    PubMed  CAS  Google Scholar 

  • Scott BB, Zaratin PF, 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(2):230–239.

    PubMed  CAS  Google Scholar 

  • Semble EL, Turner RA, et al. (1985) Rheumatoid arthritis and osteoarthritis synovial fluid effects on primary human endothelial cell cultures. J Rheumatol 12(2):237–241.

    PubMed  CAS  Google Scholar 

  • Semenza GL (2007) Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discov Today 12 (19–20):853–859.

    PubMed  CAS  Google Scholar 

  • Semenza GL (2009) Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda) 24:97–106.

    CAS  Google Scholar 

  • Senger DR, Galli SJ, et al. (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219(4587):983–985.

    PubMed  CAS  Google Scholar 

  • Shahrara S, Volin MV, et al. (2002) Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue. Arthritis Res 4(3):201–208.

    PubMed  CAS  Google Scholar 

  • Shankar J, Thippegowda PB, et al. (2009) Inhibition of HIF-1alpha activity by BP-1 ameliorates adjuvant induced arthritis in rats. Biochem Biophys Res Commun 387(2):223–228.

    PubMed  CAS  Google Scholar 

  • Shin DH, Chun YS, et al. (2008) Bortezomib inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated repression of hypoxia-inducible factor-1. Blood 111(6):3131–3136.

    PubMed  CAS  Google Scholar 

  • Sihvonen S, Korpela M, et al. (2004) Death rates and causes of death in patients with rheumatoid arthritis: a population-based study. Scand J Rheumatol 33(4):221–227.

    PubMed  CAS  Google Scholar 

  • Sivakumar B, Akhavani MA, et al. (2008) Synovial hypoxia as a cause of tendon rupture in rheumatoid arthritis. J Hand Surg [Am] 33(1):49–58.

    Google Scholar 

  • Sokka T, (2003) Work disability in early rheumatoid arthritis. Clin Exp Rheumatol 21(5 Suppl 31):S71–S74.

    PubMed  CAS  Google Scholar 

  • Solomon DH, Goodson NJ, et al. (2006) Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis 65(12):1608–1612.

    PubMed  CAS  Google Scholar 

  • Solomon DH, Karlson EW, et al. (2003) Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107(9):1303–1307.

    PubMed  Google Scholar 

  • Sone H, Kawakami Y, et al. (2001a) Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice. Biochem Biophys Res Commun 281(2):562–568.

    PubMed  CAS  Google Scholar 

  • Sone H, Sakauchi M, et al. (2001b) Elevated levels of vascular endothelial growth factor in the sera of patients with rheumatoid arthritis correlation with disease activity. Life Sci 69(16):1861–1869.

    PubMed  CAS  Google Scholar 

  • Spirig R, Potapova I, et al. (2009) TLR2 and TLR4 agonists induce production of the vasoactive peptide endothelin-1 by human dendritic cells. Mol Immunol 46:3178–3182.

    PubMed  CAS  Google Scholar 

  • Sumariwalla P, Cao Y, et al. (2003) The angiogenesis inhibitor protease-activated kringles 1-5 reduces the severity of murine collagen-induced arthritis. Arthritis Res Ther 5:R32–R39.

    PubMed  CAS  Google Scholar 

  • Taichman NS, Young S, et al. (1997) Human neutrophils secrete vascular endothelial growth factor. J Leukoc Biol 62(3):397–400.

    PubMed  CAS  Google Scholar 

  • Tanaka T, Kohno H, et al. (2000) Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats. Carcinogenesis 21(6):1183–1189.

    PubMed  CAS  Google Scholar 

  • Taylor CT (2008) Interdependent roles for hypoxia inducible factor and nuclear factor-kappaB in hypoxic inflammation. J Physiol 586(Pt 17):4055–4059.

    PubMed  CAS  Google Scholar 

  • Treuhaft PS, McCarty D (1971) Synovial fluid pH, lactate, oxygen and carbon dioxide partial pressure in various joint diseases. Arthritis Rheum 14(4):475–484.

    PubMed  CAS  Google Scholar 

  • Tubach F, Salmon D, et al. (2009) Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective french research axed on tolerance of biotherapies registry. Arthritis Rheum 60(7):1884–1894.

    PubMed  CAS  Google Scholar 

  • Uchida T, Nakashima M, et al. (2000) Immunohistochemical localisation of protein tyrosine kinase receptors Tie-1 and Tie-2 in synovial tissue of rheumatoid arthritis: Correlation with angiogenesis and synovial proliferation. Ann Rheum Dis 59(8):607–614.

    PubMed  CAS  Google Scholar 

  • van der Heijden JW, Oerlemans R, et al. (2009) The proteasome inhibitor bortezomib inhibits the release of NFkappaB-inducible cytokines and induces apoptosis of activated T cells from rheumatoid arthritis patients. Clin Exp Rheumatol 27(1):92–98.

    PubMed  Google Scholar 

  • Van Doornum S, Brand C, et al. (2006) Increased case fatality rates following a first acute cardiovascular event in patients with rheumatoid arthritis. Arthritis Rheum 54(7):2061–2068.

    PubMed  Google Scholar 

  • Walker UA (2009) More about masitinib. Arthritis Res Ther 11(4):120.

    PubMed  Google Scholar 

  • Walsh DA, Wade M, et al. (1998) Focally regulated endothelial proliferation and cell death in human synovium. Am J Pathol 152(3):691–702.

    PubMed  CAS  Google Scholar 

  • Williamson SC, Feldon P, (1995) Extensor tendon ruptures in rheumatoid arthritis. Hand Clin 11(3):449–459.

    PubMed  CAS  Google Scholar 

  • Wysocki PJ (2009) mTOR in renal cell cancer: Modulator of tumor biology and therapeutic target. Expert Rev Mol Diagn 9(3):231–241.

    PubMed  CAS  Google Scholar 

  • Yoo SA, Yoon HJ, et al. (2009) Role of placenta growth factor and its receptor flt-1 in rheumatoid inflammation: a link between angiogenesis and inflammation. Arthritis Rheum 60(2):345–354.

    PubMed  CAS  Google Scholar 

  • Yuan HT, Venkatesha S, et al. (2007) Activation of the orphan endothelial receptor Tie1 modifies Tie2-mediated intracellular signaling and cell survival. FASEB J 21(12):3171–3183.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ewa M. Paleolog .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Kiriakidis, S., Paleolog, E.M. (2010). Role of Angiogenesis in the Pathogenesis of Arthritis: Potential Therapeutic Applications. In: Slevin, M. (eds) Therapeutic Angiogenesis for Vascular Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9495-7_16

Download citation

Publish with us

Policies and ethics