Abstract
The idea of a therapeutic modality aimed at ‘starving’ a tissue of blood vessels, and consequentially of oxygen and nutrients, was born from the concept that blood vessel formation (angiogenesis) is central to the progression and maintenance of diseases which involve tissue expansion/invasion. In the first instance, solid malignancies were the target for anti-angiogenic treatments, with colorectal cancer being the first disease for which an angiogenesis inhibitor—anti-vascular endothelial growth factor antibody bevacizumab—was approved in 2004.
Our understanding of the pathogenesis of rheumatoid arthritis (RA) has lead to many parallels being drawn between this chronic inflammatory disease and solid tumours, in that both involve tissue expansion, invasion, expression of cytokines and growth factors and areas of hypoxia/hypoperfusion. As a result, angiogenesis blockade has been touted as a possible treatment for RA. The lessons learnt during the progression of eventually successful therapies such as bevacizumab should undoubtedly guide us in the future development of comparable treatments for RA.
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Paleolog EM, Miotla JM (1998) Angiogenesis in arthritis: role in disease pathogenesis and as a potential therapeutic target. Angiogenesis 2(4):295–307
Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186
Folkman J, Merler E, Abernathy C, Williams G (1971) Isolation of a tumor factor responsible for angiogenesis. J Exp Med 133(2):275–288
Lobb RR, Key ME, Alderman EM, Fett JW (1985) Partial purification and characterization of a vascular permeability factor secreted by a human colon adenocarcinoma cell line. Int J Cancer 36(4):473–478
Senger DR, Perruzzi CA, Feder J, Dvorak HF (1986) A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res 46(11):5629–5632
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306–1309
Ertel AN (1989) Flexor tendon ruptures in rheumatoid arthritis. Hand Clin 5(2):177–190
Williamson SC, Feldon P (1995) Extensor tendon ruptures in rheumatoid arthritis. Hand Clin 11(3):449–459
Walsh DA (1999) Angiogenesis and arthritis. Rheumatology (Oxford) 38(2):103–112
Koch AE (2003) Angiogenesis as a target in rheumatoid arthritis. Ann Rheum Dis 62(Suppl 2):ii60–ii67
Schumacher HR Jr, Bautista BB, Krauser RE, Mathur AK, Gall EP (1994) Histological appearance of the synovium in early rheumatoid arthritis. Semin Arthritis Rheum 23(6 Suppl 2):3–10
FitzGerald O, Bresnihan B (1995) Synovial membrane cellularity and vascularity. Ann Rheum Dis 54(6):511–515
Hirohata S, Sakakibara J (1999) Angioneogenesis as a possible elusive triggering factor in rheumatoid arthritis. Lancet 353(9161):1331
Rooney M, Condell D, Quinlan W, Daly L, Whelan A, Feighery C et al (1988) Analysis of the histologic variation of synovitis in rheumatoid arthritis. Arthritis Rheum 31(8):956–963
Ceponis A, Konttinen YT, MacKevicius Z, Solovieva SA, Hukkanen M, Tamulaitiene M et al (1996) Aberrant vascularity and von Willebrand factor distribution in inflamed synovial membrane. J Rheumatol 23(11):1880–1886
Walsh DA, Wade M, Mapp PI, Blake DR (1998) Focally regulated endothelial proliferation and cell death in human synovium. Am J Pathol 152(3):691–702
Sivakumar B, Harry LE, Paleolog EM (2004) Modulating angiogenesis: more vs. less. Jama 292(8):972–977
Sivakumar B, Paleolog EM (2005) Immunotherapy of rheumatoid arthritis: past, present and future. Curr Opin Drug Discov Devel 8(2):169–176
Bainbridge J, Sivakumar B, Paleolog E (2006) Angiogenesis as a therapeutic target in arthritis: lessons from oncology. Curr Pharm Des 12(21):2631–2644
Taylor PC, Paleolog EM (2006) Is the vasculature a potential therapeutic target in arthritis? Curr Rheumatol Rev 2(2):151–158
Sano H, Engleka K, Mathern P, Hla T, Crofford LJ, Remmers EF 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
Sano H, Forough R, Maier JA, Case JP, Jackson A, Engleka K 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
Remmers EF, Sano H, Lafyatis R, Case JP, Kumkumian GK, Hla T 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
Koch AE, Halloran MM, Hosaka S, Shah MR, Haskell CJ, Baker SK et al (1996) Hepatocyte growth factor. A cytokine mediating endothelial migration in inflammatory arthritis. Arthritis Rheum 39(9):1566–1575
Feuerherm AJ, Borset M, Seidel C, Sundan A, Leistad L, Ostensen M et al (2001) Elevated levels of osteoprotegerin (OPG) and hepatocyte growth factor (HGF) in rheumatoid arthritis. Scand J Rheumatol 30(4):229–234
Yukioka K, Inaba M, Furumitsu Y, Yukioka M, Nishino T, Goto H et al (1994) Levels of hepatocyte growth factor in synovial fluid and serum of patients with rheumatoid arthritis and release of hepatocyte growth factor by rheumatoid synovial fluid cells. J Rheumatol 21(12):2184–2189
Kusada J, Otsuka T, Matsui N, Hirano T, Asai K, Kato T (1993) Immuno-reactive human epidermal growth factor (h-EGF) in rheumatoid synovial fluids. Nippon Seikeigeka Gakkai Zasshi 67(9):859–865
Farahat MN, Yanni G, Poston R, Panayi GS (1993) Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis 52(12):870–875
Scott BB, Zaratin PF, Colombo A, Hansbury MJ, Winkler JD, Jackson JR (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
Gravallese EM, Pettit AR, Lee R, Madore R, Manning C, Tsay A 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
DeBusk LM, Chen Y, Nishishita T, Chen J, Thomas JW, Lin PC (2003) Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis. Arthritis Rheum 48(9):2461–2471
Shahrara S, Volin MV, Connors MA, Haines GK, Koch AE (2002) Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue. Arthritis Res 4(3):201–208
Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. Faseb J 13(1):9–22
Koch AE, Harlow LA, Haines GK, Amento EP, Unemori EN, Wong WL et al (1994) Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 152(8):4149–4156
Lee SS, Joo YS, Kim WU, Min DJ, Min JK, Park SH 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
Fava RA, Olsen NJ, Spencer-Green G, Yeo KT, Yeo TK, Berse B 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
Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN (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
Harada M, Mitsuyama K, Yoshida H, Sakisaka S, Taniguchi E, Kawaguchi T et al (1998) Vascular endothelial growth factor in patients with rheumatoid arthritis. Scand J Rheumatol 27(5):377–380
Kikuchi K, Kubo M, Kadono T, Yazawa N, Ihn H, Tamaki K (1998) Serum concentrations of vascular endothelial growth factor in collagen diseases. Br J Dermatol 139(6):1049–1051
Sone H, Sakauchi M, Takahashi A, Suzuki H, Inoue N, Iida K et al (2001) 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
Pufe T, Petersen W, Tillmann B, Mentlein R (2001) The splice variants VEGF121 and VEGF189 of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage. Arthritis Rheum 44(5):1082–1088
Ballara SC, Taylor PC, Reusch P, Marmé D, Feldmann M, Maini RN et al (2001) Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum 44(9):2055–2064
Latour F, Zabraniecki L, Dromer C, Brouchet A, Durroux R, Fournie B (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
Clavel G, Bessis N, Lemeiter D, Fardellone P, Mejjad O, Menard JF 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
Nakahara H, Song J, Sugimoto M, Hagihara K, Kishimoto T, Yoshizaki K et al (2003) Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthritis Rheum 48(6):1521–1529
Klimiuk PA, Sierakowski S, Domyslawska I, Fiedorczyk M, Chwiecko J (2004) Reduction of soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor levels in serum of rheumatoid arthritis patients following multiple intravenous infusions of infliximab. Arch Immunol Ther Exp (Warsz) 52(1):36–42
Aggarwal A, Panda S, Misra R (2004) Effect of etanercept on matrix metalloproteinases and angiogenic vascular endothelial growth factor: a time kinetic study. Ann Rheum Dis 63(7):891–892
Macias I, Garcia-Perez S, Ruiz-Tudela M, Medina F, Chozas N, Giron-Gonzalez JA (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
Nagashima M, Wauke K, Hirano D, Ishigami S, Aono H, Takai M 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
Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S, Ciolkiewicz M (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
Ikeda M, Hosoda Y, Hirose S, Okada Y, Ikeda E (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(4):426–433
Giatromanolaki A, Sivridis E, Athanassou N, Zois E, Thorpe PE, Brekken RA 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
Lund-Olesen K (1970) Oxygen tension in synovial fluids. Arthritis Rheum 13(6):769–776
Etherington PJ, Winlove P, Taylor P, Paleolog E, Miotla JM (2002) VEGF release is associated with reduced oxygen tensions in experimental inflammatory arthritis. Clin Exp Rheumatol 20(6):799–805
Sivakumar B (2006) Hypoxia-driven angiogensis is a key feature of tendon disease in rheumatoid arthritis. Vascul Pharmacol 45(3):e123
Hitchon C, Wong K, Ma G, Reed J, Lyttle D, El-Gabalawy H (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
Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ et al (2001) Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292(5516):468–472
Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M et al (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292(5516):464–468
Wiesener MS, Turley H, Allen WE, Willam C, Eckardt KU, Talks KL et al (1998) Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha. Blood 92(7):2260–2268
Jiang BH, Semenza GL, Bauer C, Marti HH (1996) Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol 271(4 Pt 1):C1172–C1180
Zhou J, Schmid T, Brune B (2003) Tumor necrosis factor-alpha causes accumulation of a ubiquitinated form of hypoxia inducible factor-1alpha through a nuclear factor-kappaB-dependent pathway. Mol Biol Cell 14(6):2216–2225
Scharte M, Han X, Bertges DJ, Fink MP, Delude RL (2003) Cytokines induce HIF-1 DNA binding and the expression of HIF-1-dependent genes in cultured rat enterocytes. Am J Physiol Gastrointest Liver Physiol 284(3):G373–G384
Hellwig-Burgel T, Rutkowski K, Metzen E, Fandrey J, Jelkmann W (1999) Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1. Blood 94(5):1561–1567
Albina JE, Mastrofrancesco B, Vessella JA, Louis CA, Henry WL Jr, Reichner JS (2001) HIF-1 expression in healing wounds: HIF-1alpha induction in primary inflammatory cells by TNF-alpha. Am J Physiol Cell Physiol 281(6):C1971–C1977
Bilton RL, Booker GW (2003) The subtle side to hypoxia inducible factor (HIFalpha) regulation. Eur J Biochem 270(5):791–798
Jung Y, Isaacs JS, Lee S, Trepel J, Liu ZG, Neckers L (2003) Hypoxia-inducible factor induction by tumour necrosis factor in normoxic cells requires receptor-interacting protein-dependent nuclear factor kappa B activation. Biochem J 370(Pt 3):1011–1017
Berse B, Hunt JA, Diegel RJ, Morganelli P, Yeo K, Brown F 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
Hollander AP, Corke KP, Freemont AJ, Lewis CE (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
Peters CL, Morris CJ, Mapp PI, Blake DR, Lewis CE, Winrow VR (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
Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter KC et al (2003) Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 5(4):R193–R201
Richman AI, Su EY, Ho G Jr (1981) Reciprocal relationship of synovial fluid volume and oxygen tension. Arthritis Rheum 24(5):701–705
Lee YA, Kim JY, Hong SJ, Lee SH, Yoo MC, Kim KS et al (2007). Synovial proliferation differentially affects hypoxia in the joint cavities of rheumatoid arthritis and osteoarthritis patients. Clin Rheumatol, doi: 10.1007/s10067-007-0605-2
Qu Z, Huang XN, Ahmadi P, Andresevic J, Planck SR, Hart CE et al (1995) Expression of basic fibroblast growth factor in synovial tissue from patients with rheumatoid arthritis and degenerative joint disease. Lab Invest 73(3):339–346
Salvador G, Sanmarti R, Gil-Torregrosa B, Garcia-Peiro A, Rodriguez-Cros JR, Canete JD (2006) Synovial vascular patterns and angiogenic factors expression in synovial tissue and serum of patients with rheumatoid arthritis. Rheumatology (Oxford) 45(8):966–971
Dooley S, Herlitzka I, Hanselmann R, Ermis A, Henn W, Remberger K et al (1996) Constitutive expression of c-fos and c-jun, overexpression of ets-2, and reduced expression of metastasis suppressor gene nm23-H1 in rheumatoid arthritis. Ann Rheum Dis 55(5):298–304
Trabandt A, Aicher WK, Gay RE, Sukhatme VP, Nilson-Hamilton M, Hamilton RT et al (1990) Expression of the collagenolytic and Ras-induced cysteine proteinase cathepsin L and proliferation-associated oncogenes in synovial cells of MRL/I mice and patients with rheumatoid arthritis. Matrix 10(6):349–361
Lacey D, Sampey A, Mitchell R, Bucala R, Santos L, Leech M et al (2003) Control of fibroblast-like synoviocyte proliferation by macrophage migration inhibitory factor. Arthritis Rheum 48(1):103–109
Lee MS, Yoo SA, Cho CS, Suh PG, Kim WU, Ryu SH (2006) Serum amyloid A binding to formyl peptide receptor-like 1 induces synovial hyperplasia and angiogenesis. J Immunol 177(8):5585–5594
Kim WU, Kang SS, Yoo SA, Hong KH, Bae DG, Lee MS et al (2006) Interaction of vascular endothelial growth factor 165 with neuropilin-1 protects rheumatoid synoviocytes from apoptotic death by regulating Bcl-2 expression and Bax translocation. J Immunol 177(8):5727–5735
Miagkov AV, Kovalenko DV, Brown CE, Didsbury JR, Cogswell JP, Stimpson SA et al (1998) NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc Natl Acad Sci USA 95(23):13859–13864
Schedel J, Gay RE, Kuenzler P, Seemayer C, Simmen B, Michel BA et al (2002) FLICE-inhibitory protein expression in synovial fibroblasts and at sites of cartilage and bone erosion in rheumatoid arthritis. Arthritis Rheum 46(6):1512–1518
Meinecke I, Cinski A, Baier A, Peters MA, Dankbar B, Wille A et al (2007) Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts. Proc Natl Acad Sci USA 104(12):5073–5078
Seemayer CA, Kuchen S, Kuenzler P, Rihoskova V, Rethage J, Aicher WK et al (2003) Cartilage destruction mediated by synovial fibroblasts does not depend on proliferation in rheumatoid arthritis. Am J Pathol 162(5):1549–1557
Mohr W, Beneke G, Mohing W (1975) Proliferation of synovial lining cells and fibroblasts. Ann Rheum Dis 34(3):219–224
Baier A, Meineckel I, Gay S, Pap T (2003) Apoptosis in rheumatoid arthritis. Curr Opin Rheumatol 15(3):274–279
Ho QT, Kuo CJ (2007) Vascular endothelial growth factor: biology and therapeutic applications. Int J Biochem Cell Biol 39(7–8):1349–1357
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967
Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M et al (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85(3):221–228
Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. Embo J 18(14):3964–3972
Murayama T, Tepper OM, Silver M, Ma H, Losordo DW, Isner JM et al (2002) Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol 30(8):967–972
Hattori K, Dias S, Heissig B, Hackett NR, Lyden D, Tateno M et al (2001) Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 193(9):1005–1014
Ruger B, Giurea A, Wanivenhaus AH, Zehetgruber H, Hollemann D, Yanagida G et al (2004) Endothelial precursor cells in the synovial tissue of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum 50(7):2157–2166
Grisar J, Aletaha D, Steiner CW, Kapral T, Steiner S, Seidinger D et al (2005) Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 111(2):204–211
Herbrig K, Haensel S, Oelschlaegel U, Pistrosch F, Foerster S, Passauer J (2005) Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann Rheum Dis 65(2):157–163
Hirohata S, Yanagida T, Nampei A, Kunugiza Y, Hashimoto H, Tomita 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
Ablin JN, Boguslavski V, Aloush V, Elkayam O, Paran D, Caspi D et al (2006) Effect of anti-TNFalpha treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis. Life Sci 79(25):2364–2369
Van Doornum S, McColl G, Wicks IP (2002) Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum 46(4):862–873
Van Doornum S, Brand C, King B, Sundararajan V (2006) Increased case fatality rates following a first acute cardiovascular event in patients with rheumatoid arthritis. Arthritis Rheum 54(7):2061–2068
Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H et al (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):E1–E7
Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA et al (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348(7):593–600
Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U et al (2005) Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 111(22):2981–2987
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A et al (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353(10):999–1007
Grisar JC, Aletaha D, Steiner CW, Kapral T, Steiner S, Saemann M et al (2007) Endothelial progenitor cells in active rheumatoid arthritis: Effects of TNF and of glucocorticoid therapy. Ann Rheum Dis, doi: 10.1136/ard.2006.066605
Seeger FH, Haendeler J, Walter DH, Rochwalsky U, Reinhold J, Urbich C et al (2005) p38 mitogen-activated protein kinase downregulates endothelial progenitor cells. Circulation 111(9):1184–1191
Taylor PC, Sivakumar B (2005) Hypoxia and angiogenesis in rheumatoid arthritis. Curr Opin Rheumatol 17(3):293–298
Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18(3):581–592
Statistics OfN. Mortality Statistics: Cause. England and Wales 2005. London TSO 2006
Campbell NC, Elliott AM, Sharp L, Ritchie LD, Cassidy J, Little J (2001) Rural and urban differences in stage at diagnosis of colorectal and lung cancers. Br J Cancer 84(7):910–914
Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676
Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ (1995) Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 147(1):33–41
Kuwai T, Kitadai Y, Tanaka S, Onogawa S, Matsutani N, Kaio E et al (2003) Expression of hypoxia-inducible factor-1alpha is associated with tumor vascularization in human colorectal carcinoma. Int J Cancer 105(2):176–181
Konerding MA, Malkusch W, Klapthor B, van Ackern C, Fait E, Hill SA et al (1999) Evidence for characteristic vascular patterns in solid tumours: quantitative studies using corrosion casts. Br J Cancer 80(5–6):724–732
Denekamp J (1990) Vascular attack as a therapeutic strategy for cancer. Cancer Metastasis Rev 9(3):267–282
Wouters BG, Weppler SA, Koritzinsky M, Landuyt W, Nuyts S, Theys J et al (2002) Hypoxia as a target for combined modality treatments. Eur J Cancer 38(2):240–257
Goethals L, Debucquoy A, Perneel C, Geboes K, Ectors N, De Schutter H et al (2006) Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and potential intrinsic hypoxia markers. Int J Radiat Oncol Biol Phys 65(1):246–254
Zakarija A, Soff G (2005) Update on angiogenesis inhibitors. Curr Opin Oncol 17(6):578–583
Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L et al (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57(20):4593–4599
Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7(9):987–989
Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10(2):145–147
Koukourakis MI, Mavanis I, Kouklakis G, Pitiakoudis M, Minopoulos G, Manolas C et al (2007) Early antivascular effects of bevacizumab anti-VEGF monoclonal antibody on colorectal carcinomas assessed with functional CT imaging. Am J Clin Oncol 30(3):315–318
Yao K, Gietema JA, Shida S, Selvakumaran M, Fonrose X, Haas NB et al (2005) In vitro hypoxia-conditioned colon cancer cell lines derived from HCT116 and HT29 exhibit altered apoptosis susceptibility and a more angiogenic profile in vivo. Br J Cancer 93(12):1356–1363
Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G et al (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21(1):60–65
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342
Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 23(16):3706–3712
Giantonio BJ, Levy DE, O’Dwyer P J, Meropol NJ, Catalano PJ, Benson AB 3rd (2006) A phase II study of high-dose bevacizumab in combination with irinotecan, 5-fluorouracil, leucovorin, as initial therapy for advanced colorectal cancer: results from the Eastern Cooperative Oncology Group study E2200. Ann Oncol 17(9):1399–1403
Wood JM, Bold G, Buchdunger E, Cozens R, Ferrari S, Frei J et al (2000) PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 60(8):2178–2189
Hecht J, Trarbach T, Jaeger E, Hainsworth J, Wolff R, Lloyd K et al (2005) A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/ 5-fluorouracil. J Clin Oncol 2005 ASCO Annual Meeting Proceedings 23(16S, Part I of II (June 1 Supplement)):3
Koehne C, Bajetta E, Lin E, Van Cutsem E, Hecht J, Douillard J et al (2006) Results of an interim analysis of a multinational randomized, double-blind, phase III study in patients (pts) with previously treated metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo (CONFIRM 2). J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I 24(No. 18S (June 20 Supplement), 2006):3508
Major P, Trarbach T, Lenz H, Kerr D, Pendergrass K, Douillard J et al (2006) A meta-analysis of two randomized, double-blind, placebo-controlled, phase III studies in patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK/ZK to determine clinical benefit on progression-free survival (PFS) in high LDH pts. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I 24(No. 18S (June 20 Supplement)):3529
Jost LM, Gschwind HP, Jalava T, Wang Y, Guenther C, Souppart C et al (2006) Metabolism and disposition of vatalanib (PTK787/ZK-222584) in cancer patients. Drug Metab Dispos 34(11):1817–1828
Malemud CJ (2007) Growth hormone, VEGF and FGF: involvement in rheumatoid arthritis. Clin Chim Acta 375(1–2):10–19
Berry S, Cunningham D, Michael M, Dibartolomeo M, Rivera F, Kretzschmar A et al (2006) Preliminary safety of bevacizumab with first-line Folfox, Capox, Folfiri and capecitabine for mCRC-First B.E.A.Trial. J Clin Oncol, ASCO Annual Meeting Proceedings Part I 24(No. 18S (June 20 Supplement)):3534
Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J et al (2005) Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91(3):173–180
Tabruyn SP, Griffioen AW (2007) Molecular pathways of angiogenesis inhibition. Biochem Biophys Res Commun 355(1):1–5
Williams RO (2007) Collagen-induced arthritis in mice: a major role for tumor necrosis factor-alpha. Methods Mol Biol (Clifton, NJ 361:265–284
Holmdahl R, Jansson L, Larsson E, Rubin K, Klareskog L (1986) Homologous type II collagen induces chronic and progressive arthritis in mice. Arthritis Rheum 29(1):106–113
Malfait AM, Williams RO, Malik AS, Maini RN, Feldmann M (2001) Chronic relapsing homologous collagen-induced arthritis in DBA/1 mice as a model for testing disease-modifying and remission-inducing therapies. Arthritis Rheum 44(5):1215–1224
Williams RO, Ghrayeb J, Feldmann M, Maini RN (1995) Successful therapy of collagen-induced arthritis with TNF receptor-IgG fusion protein and combination with anti-CD4. Immunology 84(3):433–439
Williams RO, Marinova-Mutafchieva L, Feldmann M, Maini RN (2000) Evaluation of TNF-alpha and IL-1 blockade in collagen-induced arthritis and comparison with combined anti-TNF-alpha/anti-CD4 therapy. J Immunol 165(12):7240–7245
Williams RO, Mason LJ, Feldmann M, Maini RN (1994) Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis. Proc Natl Acad Sci USA 91(7):2762–2766
Lu J, Kasama T, Kobayashi K, Yoda Y, Shiozawa F, Hanyuda M et al (2000) Vascular endothelial growth factor expression and regulation of murine collagen-induced arthritis. J Immunol 164(11):5922–5927
Sone H, Kawakami Y, Sakauchi M, Nakamura Y, Takahashi A, Shimano H et al (2001) Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice. Biochem Biophys Res Commun 281(2):562–568
Miotla J, Maciewicz R, Kendrew J, Feldmann M, Paleolog E (2000) Treatment with soluble VEGF receptor reduces disease severity in murine collagen-induced arthritis. Lab Invest 80(8):1195–1205
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(23):1950–1960
de Bandt M, Ben Mahdi MH, Ollivier V, Grossin M, Dupuis M, Gaudry M 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
Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F 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
Grosios K, Wood J, Esser R, Raychaudhuri A, Dawson J (2004) Angiogenesis inhibition by the novel VEGF receptor tyrosine kinase inhibitor, PTK787/ZK222584, causes significant anti-arthritic effects in models of rheumatoid arthritis. Inflamm Res 53(4):133–142
Clauss M, Weich H, Breier G, Knies U, Rockl W, Waltenberger J et al (1996) The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J Biol Chem 271(30):17629–17634
Sawano A, Iwai S, Sakurai Y, Ito M, Shitara K, Nakahata T et al (2001) Flt-1, vascular endothelial growth factor receptor 1, is a novel cell surface marker for the lineage of monocyte-macrophages in humans. Blood 97(3):785–791
Murakami M, Iwai S, Hiratsuka S, Yamauchi M, Nakamura K, Iwakura Y et al (2006) Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocytes/macrophages. Blood 108(6):1849–1856
Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M et al (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573):435–439
Mould AW, Tonks ID, Cahill MM, Pettit AR, Thomas R, Hayward NK et al (2003) Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis. Arthritis Rheum 48(9):2660–2669
Autiero M, Luttun A, Tjwa M, Carmeliet P (2003) Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J Thromb Haemost 1(7):1356–1370
Tjwa M, Luttun A, Autiero M, Carmeliet P (2003) VEGF and PlGF: two pleiotropic growth factors with distinct roles in development and homeostasis. Cell Tissue Res 314(1):5–14
Autiero M, Waltenberger J, Communi D, Kranz A, Moons L, Lambrechts D 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
Oosthuyse B, Moons L, Storkebaum E, Beck H, Nuyens D, Brusselmans K et al (2001) Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 28(2):131–138
Bottomley MJ, Webb NJ, Watson CJ, Holt L, Bukhari M, Denton J 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
Date K, Matsumoto K, Shimura H, Tanaka M, Nakamura T (1997) HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. FEBS Lett 420(1):1–6
Kuba K, Matsumoto K, Date K, Shimura H, Tanaka M, Nakamura T (2000) HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice. Cancer Res 60(23):6737–6743
Nakabayashi M, Morishita R, Nakagami H, Kuba K, Matsumoto K, Nakamura T et al (2003) HGF/NK4 inhibited VEGF-induced angiogenesis in in vitro cultured endothelial cells and in vivo rabbit model. Diabetologia 46(1):115–123
Matsumoto K, Nakamura T (2005) Mechanisms and significance of bifunctional NK4 in cancer treatment. Biochem Biophys Res Commun 333(2):316–327
Kim JM, Ho SH, Park EJ, Hahn W, Cho H, Jeong JG et al (2002) Angiostatin gene transfer as an effective treatment strategy in murine collagen-induced arthritis. Arthritis Rheum 46(3):793–801
Kato K, Miyake K, Igarashi T, Yoshino S, Shimada T (2005) Human immunodeficiency virus vector-mediated intra-articular expression of angiostatin inhibits progression of collagen-induced arthritis in mice. Rheumatol Int 25(7):522–529
Takahashi H, Kato K, Miyake K, Hirai Y, Yoshino S, Shimada T (2005) Adeno-associated virus vector-mediated anti-angiogenic gene therapy for collagen-induced arthritis in mice. Clin Exp Rheumatol 23(4):455–461
Sumariwalla P, Cao Y, Wu H, Feldmann M, Paleolog E (2003) The angiogenesis inhibitor protease-activated kringles 1–5 reduces the severity of murine collagen-induced arthritis. Arthritis Res Ther 5:R32–R39
Matsuno H, Yudoh K, Uzuki M, Nakazawa F, Sawai T, Yamaguchi N et al (2002) Treatment with the angiogenesis inhibitor endostatin: a novel therapy in rheumatoid arthritis. J Rheumatol 29(5):890–895
Yin G, Liu W, An P, Li P, Ding I, Planelles V et al (2002) Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis. Mol Ther 5(5 Pt 1):547–554
Kurosaka D, Yoshida K, Yasuda J, Yokoyama T, Kingetsu I, Yamaguchi N et al (2003) Inhibition of arthritis by systemic administration of endostatin in passive murine collagen induced arthritis. Ann Rheum Dis 62(7):677–679
Yue L, Shen YX, Feng LJ, Chen FH, Yao HW, Liu LH et al (2007) Blockage of the formation of new blood vessels by recombinant human endostatin contributes to the regression of rat adjuvant arthritis. Eur J Pharmacol 567(1–2):166–170
de Bandt M, Grossin M, Weber AJ, Chopin M, Elbim C, Pla 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
Arsenault AL, Lhotak S, Hunter WL, Banquerigo ML, Brahn E (1998) Taxol involution of collagen-induced arthritis: ultrastructural correlation with the inhibition of synovitis and neovascularization. Clin Immunol Immunopathol 86(3):280–289
Peacock DJ, Banquerigo ML, Brahn E (1992) Angiogenesis inhibition suppresses collagen arthritis. J Exp Med 175(4):1135–1138
Peacock DJ, Banquerigo ML, Brahn E (1995) A novel angiogenesis inhibitor suppresses rat adjuvant arthritis. Cell Immunol 160(2):178–184
Oliver SJ, Banquerigo ML, Brahn E (1994) Suppression of collagen-induced arthritis using an angiogenesis inhibitor, AGM-1470, and a microtubule stabilizer, taxol. Cell Immunol 157(1):291–299
Oliver SJ, Cheng TP, Banquerigo ML, Brahn E (1995) Suppression of collagen-induced arthritis by an angiogenesis inhibitor, AGM-1470, in combination with cyclosporin: reduction of vascular endothelial growth factor (VEGF). Cell Immunol 166(2):196–206
Nagashima M, Tanaka H, Takahashi H, Tachihara A, Tanaka K, Ishiwata T et al (2002) Study of the mechanism involved in angiogenesis and synovial cell proliferation in human synovial tissues of patients with rheumatoid arthritis using SCID mice. Lab Invest 82(8):981–988
Bernier SG, Lazarus DD, Clark E, Doyle B, Labenski MT, Thompson CD 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
Bernier SG, Taghizadeh N, Thompson CD, Westlin WF, Hannig G (2005) Methionine aminopeptidases type I and type II are essential to control cell proliferation. J Cell Biochem 95(6):1191–1203
Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP et al (1994) The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 368(6468):237–239
Ireson CR, Chander SK, Purohit A, Perera S, Newman SP, Parish D et al (2004) Pharmacokinetics and efficacy of 2-methoxyoestradiol and 2-methoxyoestradiol-bis-sulphamate in vivo in rodents. Br J Cancer 90(4):932–937
Holmdahl R, Jansson L, Meyerson B, Klareskog L (1987) Oestrogen induced suppression of collagen arthritis: I. Long term oestradiol treatment of DBA/1 mice reduces severity and incidence of arthritis and decreases the anti type II collagen immune response. Clin Exp Immunol 70(2):372–378
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
Acknowledgements
The Kennedy Institute of Rheumatology receives a core grant from Arthritis Research Campaign (Registered Charity No. 207711). The authors are grateful for the support of the Marie Curie Research Training Network EURO-RA, funded by the Sixth Framework Programme of the European Union (HL and YR).
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Khong, T.L., Larsen, H., Raatz, Y. et al. Angiogenesis as a therapeutic target in arthritis: learning the lessons of the colorectal cancer experience. Angiogenesis 10, 243–258 (2007). https://doi.org/10.1007/s10456-007-9081-1
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DOI: https://doi.org/10.1007/s10456-007-9081-1