mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2014-2-71-75mrj-550Research ArticleОБЗОРЫREVIEWSАнгиогенез при псориазе и псориатическом артрите: клеточные и гуморальные механизмы, роль в патогенезе и поиск перспективных мишеней терапииAngiogenesis in patients with psoriasis and psoriatic arthritis: cell-mediated and humoral mechanisms, its role in pathogenesis, and searching for promising therapeutic targetsКоротаеваТ.В.KorotaevaT.V.1@ru.ruФГБУ «Научно-исследовательский иститут ревматологии им. В.А. Насоновой» РАМН, Москва, РоссияРоссияV.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, RussiaRussian Federation201408052014827175Copyright © Коротаева Т., 20142014Коротаева Т.Korotaeva T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/550

Проанализированы современные представления о роли ангиогенеза в патогенезе псориаза и псориатического артрита (ПсА). Рассмотрены особенности клеточных и гуморальных реакций, приводящие к развитию пролиферации синовиальной оболочки и разрастанию в ней сосудов при данной патологии. Показано, что в прогрессировании процессов неоваскуляризации участвуют ряд медиаторов ангиогенеза, проангиогеннные цитокины, факторы роста, матриксные металлопротеиназы и др. Обращено внимание на роль фактора некроза опухоли α как важнейшей мишени таргетной терапии псориаза и ПсА, рассмотрены лекарственные средства, используемые или разрабатываемые для этой цели, блокирующие некоторые звенья ангиогенеза. 

Modern concepts of the role of angiogenesis in pathogenesis of psoriasis and psoriatic arthritis (PsA) are analyzed. The features of cell-mediated and humoral immune responses resulting in proliferation of synovial membrane and vessel overgrowth in patients with this pathology are discussed. A number of angiogenesis mediators, pro-angiogenic cytokines, growth factors, matrix metalloproteinases, etc. are shown to be involved in progression of neovascularization. The role of tumor necrosis factor α as a key therapeutic target for treatment of psoriasis and PsA is emphasized. Drugs inhibiting some stages of angiogenesis, which are either used in clinical practice or are being developed, are discussed. 

псориатический артритпсориазангиогенезиммунологические механизмыпроангиогенные цитокиныфакто- ры ростафактор некроза опухоли α.psoriatic arthritispsoriasisangiogenesisimmunological mechanismspro-angiogenic cytokinesgrowth factorstumor necrosis factor α.ReferencesNestle F, Gilliet M. Defining upstream elements of psoriasis pathogenesis: an emerging role for interferon α. J Invest Dermatol. 2005;125(5):14–5. DOI: http://dx.doi.org/10.1111/j.0022-202X.2005.23923.x.Nestle F, Gilliet M. Defining upstream elements of psoriasis pathogenesis: an emerging role for interferon α. J Invest Dermatol. 2005;125(5):14–5. DOI: http://dx.doi.org/10.1111/j.0022-202X.2005.23923.x.Fearon U, Griosios K, Fraser A, et al. Angiopoietins, growth factors, and vascular morphology in early arthritis. J Rheumatol. 2003;30(2):260–8.Fearon U, Griosios K, Fraser A, et al. Angiopoietins, growth factors, and vascular morphology in early arthritis. J Rheumatol. 2003;30(2):260–8.Ancelin M, Chollet-Martin S, Herve M, et al. Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in extravascular tissue via an autocrine amplification mechanism. Lab Invest. 2004;84(4):502–12. DOI: http://dx.doi.org/10.1038/labinvest.3700053.Ancelin M, Chollet-Martin S, Herve M, et al. Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in extravascular tissue via an autocrine amplification mechanism. Lab Invest. 2004;84(4):502–12. DOI: http://dx.doi.org/10.1038/labinvest.3700053.Rosenberger C, Solovan C, Rosenberger A, et al. Upregulation of hypoxia-inducible factors in normal and psoriatic skin. J Invest Dermatol. 2007;127(10):2445–52. DOI: http://dx.doi.org/10.1038/sj.jid.5700874.Rosenberger C, Solovan C, Rosenberger A, et al. Upregulation of hypoxia-inducible factors in normal and psoriatic skin. J Invest Dermatol. 2007;127(10):2445–52. DOI: http://dx.doi.org/10.1038/sj.jid.5700874.Detmar M, Brown L, Schon B, et al. Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol. 1998;111(1):1–6. DOI: http://dx.doi.org/10.1046/j.1523-1747.1998.00262.x.Detmar M, Brown L, Schon B, et al. Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. J Invest Dermatol. 1998;111(1):1–6. DOI: http://dx.doi.org/10.1046/j.1523-1747.1998.00262.x.Voskas D, Jones N, Van Slyke P, et al. A cyclosporine-sensitive psoriasis-like disease produced in Tie2 transgenic mice. Am JVoskas D, Jones N, Van Slyke P, et al. A cyclosporine-sensitive psoriasis-like disease produced in Tie2 transgenic mice. Am JPathol. 2005;166(3):843–55. DOI: http://dx.doi.org/10.1016/S0002-9440(10)62305-X.Pathol. 2005;166(3):843–55. DOI: http://dx.doi.org/10.1016/S0002-9440(10)62305-X.Singh T, Schon B, Wallbrecht K, et al. Involvement of IL-9 inTh17-associated inflammation and angiogenesis of psoriasis. PLOS One. 2013;8(1):e51752. DOI: 10.1371 /journal.pone.0051752. Epub 2013 Jan 15.Singh T, Schon B, Wallbrecht K, et al. Involvement of IL-9 inTh17-associated inflammation and angiogenesis of psoriasis. PLOS One. 2013;8(1):e51752. DOI: 10.1371 /journal.pone.0051752. Epub 2013 Jan 15.Zibert J, Wallbrecht K, Schon M, et al. Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions. J Clin Invest. 2011;121(1):410–21. DOI: http://dx.doi.org/10.1172/JCI41295.Zibert J, Wallbrecht K, Schon M, et al. Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions. J Clin Invest. 2011;121(1):410–21. DOI: http://dx.doi.org/10.1172/JCI41295.Abe R, Yamagishi S, Fujita Y, et al. Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis. J Dermatol Scien. 2010;57(3):183–91. DOI: http://dx.doi.org/ 10.1016/j.jdermsci.2009.12.010.Abe R, Yamagishi S, Fujita Y, et al. Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis. J Dermatol Scien. 2010;57(3):183–91. DOI: http://dx.doi.org/ 10.1016/j.jdermsci.2009.12.010.Yamamoto T, Yokozeki H, Nishioka K. Clinical analysis of 21 patients with psoriasis arthropathy. J Dermatol. 2005;32(2):84–90.Yamamoto T, Yokozeki H, Nishioka K. Clinical analysis of 21 patients with psoriasis arthropathy. J Dermatol. 2005;32(2):84–90.Borgato L, Puccetti A, Beri R. The T cell receptor repertoire in psoriatic synovitis is restricted and T lymphocytes expressing the same TCR are present in joint and skin lesions. J Rheumatol. 2002;29(9):1914–9.Borgato L, Puccetti A, Beri R. The T cell receptor repertoire in psoriatic synovitis is restricted and T lymphocytes expressing the same TCR are present in joint and skin lesions. J Rheumatol. 2002;29(9):1914–9.Flytlie H, Hvid M, Lindgreen E, et al. Expression of MDC/ CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis and osteoarthritis. Cytok. 2010;49(1):24–9. DOI: http://dx.doi.org/10.1016/j.cyto.2009.10.005.Flytlie H, Hvid M, Lindgreen E, et al. Expression of MDC/ CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis and osteoarthritis. Cytok. 2010;49(1):24–9. DOI: http://dx.doi.org/10.1016/j.cyto.2009.10.005.Van Kuijk A, Reinders-Blankert P, Smeets T, et al. Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis. 2006;65(12):1551–7. DOI: http://dx.doi.org/10.1136/ard.2005.050963.Van Kuijk A, Reinders-Blankert P, Smeets T, et al. Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis. 2006;65(12):1551–7. DOI: http://dx.doi.org/10.1136/ard.2005.050963.Di Cesare A, Di Meglio P, Nestle F. The IL-23Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129(6):1339–50. DOI: http://dx.doi.org/10.1038/jid.2009.59.Di Cesare A, Di Meglio P, Nestle F. The IL-23Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129(6):1339–50. DOI: http://dx.doi.org/10.1038/jid.2009.59.Wolk K, Haugen H, Xu W, et al. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-α are not. J Molec Med. 2009;87(5):523–36. DOI: http://dx.doi.org/10.1007/s00109-009-0457-0.Wolk K, Haugen H, Xu W, et al. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-α are not. J Molec Med. 2009;87(5):523–36. DOI: http://dx.doi.org/10.1007/s00109-009-0457-0.Hedrick M., Lonsdorf A., Shirakawa A, et al. CCR6 is required for IL-23-induced psoriasis-like inflammation in mice. J Clin Invest. 2009;119(8):2317–29. http://dx.doi.org/10.1172/JCI37378.Hedrick M., Lonsdorf A., Shirakawa A, et al. CCR6 is required for IL-23-induced psoriasis-like inflammation in mice. J Clin Invest. 2009;119(8):2317–29. http://dx.doi.org/10.1172/JCI37378.Curtsinger J, Valenzuela J, Agarwal P, et al. Cutting edge: type I IFNs provide a third signal to CD8 T cells to stimulate clonal xpansion and differentiation. J Immunol. 2005;174(8):4465–69.Curtsinger J, Valenzuela J, Agarwal P, et al. Cutting edge: type I IFNs provide a third signal to CD8 T cells to stimulate clonal xpansion and differentiation. J Immunol. 2005;174(8):4465–69.Koczulla R, Von Degenfeld G, Kupatt C, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003;111(11):1665–72. DOI: http://dx.doi.org/10.1172/JCI17545.Koczulla R, Von Degenfeld G, Kupatt C, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003;111(11):1665–72. DOI: http://dx.doi.org/10.1172/JCI17545.Lande R, Giacomini E, Serafini B, et al. Characterization and recruitment of plasmacytoid dendritic cells in synovial fluid and tissue of patients with chronic inflammatory arthritis. J Immunol. 2004;173(4):2815–24.Lande R, Giacomini E, Serafini B, et al. Characterization and recruitment of plasmacytoid dendritic cells in synovial fluid and tissue of patients with chronic inflammatory arthritis. J Immunol. 2004;173(4):2815–24.Wenzel J, Worenk E, Freutel S, et al. Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus. J Pathol. 2005;205(4);435–2. DOI: http://dx.doi.org/10.1002/path.1721.Wenzel J, Worenk E, Freutel S, et al. Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus. J Pathol. 2005;205(4);435–2. DOI: http://dx.doi.org/10.1002/path.1721.Yamamoto T, Matsuuchi M, Watanabe K, et al. Mast cells in the synovium of patients with psoriasis arthropathy. Dermatol. 1997;195(1):73–4. DOI: http://dx.doi.org/10.1159/000245694.Yamamoto T, Matsuuchi M, Watanabe K, et al. Mast cells in the synovium of patients with psoriasis arthropathy. Dermatol. 1997;195(1):73–4. DOI: http://dx.doi.org/10.1159/000245694.Walsh L, Trinchieri G, Waldorf H, et al. Human dermal mast cells contain and release tumor necrosis factor α,which induces endothelial leukocyte adhesion 6 ISRN Dermatology molecule 1. Proc Nat Acad Scien USA. 1991;88(10):4220–4. DOI: http://dx.doi.org/10.1073/pnas.88.10.4220.Walsh L, Trinchieri G, Waldorf H, et al. Human dermal mast cells contain and release tumor necrosis factor α,which induces endothelial leukocyte adhesion 6 ISRN Dermatology molecule 1. Proc Nat Acad Scien USA. 1991;88(10):4220–4. DOI: http://dx.doi.org/10.1073/pnas.88.10.4220.Reece R, Canete J, Parsons W, et al. Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthritis. Arthritis Rheum. 1999;42(7):1481–4. DOI: http://dx.doi.org/10.1002/1529-0131(199907)42:7%3C1481::AID-ANR23%3E3.0.CO;2-E.Reece R, Canete J, Parsons W, et al. Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthritis. Arthritis Rheum. 1999;42(7):1481–4. DOI: http://dx.doi.org/10.1002/1529-0131(199907)42:7%3C1481::AID-ANR23%3E3.0.CO;2-E.Veale D, Ritchlin C, FitzGerald O. Immunopathology of psoriasis and psoriatic arthritis. Ann Rheum Dis. 2005;64 Suppl 2:26–9. DOI: http://dx.doi.org/10.1136/ard.2004.031740.Veale D, Ritchlin C, FitzGerald O. Immunopathology of psoriasis and psoriatic arthritis. Ann Rheum Dis. 2005;64 Suppl 2:26–9. DOI: http://dx.doi.org/10.1136/ard.2004.031740.Mastroianni A, Minutilli E, Mussi A, et al. Cytokine profiles during infliximab monotherapy in psoriatic arthritis. Br J Dermatol. 2005;153(3):531–6. DOI: http://dx.doi.org/10.1111/j.1365-2133.2005.06648.x.Mastroianni A, Minutilli E, Mussi A, et al. Cytokine profiles during infliximab monotherapy in psoriatic arthritis. Br J Dermatol. 2005;153(3):531–6. DOI: http://dx.doi.org/10.1111/j.1365-2133.2005.06648.x.Cordiali-Fei P, Trento E, D’Agosto E, et al. Effective therapy with anti-TNF-α in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions. Ann NY Acad Scien. 2007;1110:578–89. DOI: http://dx.doi.org/10.1196/annals.1423.062.Cordiali-Fei P, Trento E, D’Agosto E, et al. Effective therapy with anti-TNF-α in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions. Ann NY Acad Scien. 2007;1110:578–89. DOI: http://dx.doi.org/10.1196/annals.1423.062.Ritchlin C, Kavanaugh A, Gladman D, et al. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis. 2009;68(9):1387–94. DOI: 10.1136/ard.2008.094946. Epub 2008 Oct 24.Ritchlin C, Kavanaugh A, Gladman D, et al. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis. 2009;68(9):1387–94. DOI: 10.1136/ard.2008.094946. Epub 2008 Oct 24.Kavanaugh A, Menter A, Mendelsohn A, et al. Effect of ustekinumab on physical function and health-related quality of life in patients with psoriatic arthritis: a randomized, placebo-controlled, phase II trial. Curr Med Res Opin. 2010;26(10):2385–92. DOI: 10.1185/03007995.2010.515804.Kavanaugh A, Menter A, Mendelsohn A, et al. Effect of ustekinumab on physical function and health-related quality of life in patients with psoriatic arthritis: a randomized, placebo-controlled, phase II trial. Curr Med Res Opin. 2010;26(10):2385–92. DOI: 10.1185/03007995.2010.515804.Rozenblit M, Lebwohl M. New biologics for psoriasis and psoriatic arthritis. Dermatol Ther. 2009;22(1):56–60. DOI: 10.1111/j.1529-8019.2008.01216.x.Rozenblit M, Lebwohl M. New biologics for psoriasis and psoriatic arthritis. Dermatol Ther. 2009;22(1):56–60. DOI: 10.1111/j.1529-8019.2008.01216.x.Heidenreich R, Rocken M., Ghoreschi K. Angiogenesis drives psoriasis pathogenesis. Int J Exp Path. 2009;90(3):232–48. DOI: 10.1111/j.1365-2613.2009.00669.x.Heidenreich R, Rocken M., Ghoreschi K. Angiogenesis drives psoriasis pathogenesis. Int J Exp Path. 2009;90(3):232–48. DOI: 10.1111/j.1365-2613.2009.00669.x.

The authors declare that there are no conflicts of interest present.