Review Article
 

Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis

Abstract

Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis.

1. Carmeliet P. Angiogenesis in life, disease and medicine.Nature 2005; 438(7070):932–6.

2. Manetti M, Guiducci S, Ibba-Manneschi L, Matucci- Cerinic M. Mechanisms in the loss of capillaries in systemic sclerosis: angiogenesis versus vasculogenesis. J Cell Mol Med 2010; 14(6A):1241-54.

3. Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S, Distler O. Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med 2003; 47(3):149–61.

4. Tahergorabi Z, Khazaei M. A Review on Angiogenesis and Its Assays. Iran J Basic Med Sci 2012; 15(6):1110-26.

5. Mueller MM. Inflammation and angiogenesis: innate immune cells as modulators of tumor vascularization. In: Marmé D, Fusenig N, editors. Tumor angiogenesis. Basic mechanisms and cancer therapy. Berlin-Heidelberg: Springer-Verlag 2008:351–62.

6. Seabrook TJ, Littlewood-Evans A, Brinkmann V, Pöllinger B, Schnell C, Hiestand PC. Angiogenesis is present in experimental autoimmune encephalomyelitis and pro-angiogenic factors increase in multiple sclerosis lesions. J Neuroinflammation 2010; 7:95.

7. Kirk S, Frank JA, Karlik S. Angiogenesis in multiple sclerosis: is it good, bad or an epiphenomenon? J Neurol Sci 2004; 217(2):125–30.

8. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000;343(13):938–52.

9. Mirshafiey A. Venom therapy in multiple sclerosis.Neuropharmacology 2007; 53(3):353-61.

10. Holley JE, Newcombe J, Whatmore JL, Gutowski NJ.Increased blood vessel density and endothelial cell proliferation in multiple sclerosis cerebral white matter. Neurosci Lett 2010; 470(1):65-70.

11. Mirshafiey A, Mohsenzadegan M. Immunotoxicological effects of reactive oxygen species in multiple sclerosis. Journal on Chinese Clinical Medicine 2008; 3:405-11.

12. Silvestre JS, Levy BI, Tedgui A. Mechanisms of angiogenesis and remodeling of the microvasculature. Cardiovasc Res 2008; 78(2): 201–2.

13. Sainson RC, Aoto J, Nakatsu MN, Holderfield M, Conn E, Koller E, et al. Cell-autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis. FASEB J 2005; 19(8):1027-9.

14. Radtke F, Schweisguth F, Pear W. The Notch 'gospel'.EMBO Rep 2005; 6(12):1120-5.

15. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, et al. VEGF guides angiogenic sprouting utilizes endothelial tip cell filopodia. J Cell Biol 2003; 161(6):1163-77.

16. Jain RK. Molecular regulation of vessel maturation. Nat Med 2003; 9(6):685-93.

17. Betsholtz C. Insight into the physiological functions of PDGF through genetic studies in mice. Cytokine Growth Factor Rev 2004; 15(4):215-28.

18. Fredriksson L, Li H, Eriksson U. 2004. The PDGF family: four gene products from five dimeric isoforms. Cytokine Growth Factor Rev 2004; 15(4):197-204.

19. Salehi E, Amjadi F, Khazaei M. Angiogenesis in health and disease: Role of vascular endothelial growth factor (VEGF) J Isfahan Med School 2011; 29:1-15.

20. Rigau V, Morin M, Rousset MC, de BF, Lebrun A, Coubes P, et al. Angiogenesis is associated with blood- brain barrier permeability in temporal lobe epilepsy. Brain 2007; 130(Pt 7):1942–56.

21. Ribatti D, Crivellato E. Immune cells and angiogenesis J Cell Mol Med 2009; 13(9A):2822-33.

22. MacMillan CJ, Starkey RJ, Easton AS. Angiogenesis is regulated by angiopoietin during experimental autoimmune encephalomyelitis and is indirectly related to vascular permeability. J Neuropathol Exp Neurol 2011;70(12):1107–23.

23. MacMillan CJ, Furlong SJ, Doucette CD, Chen PL, Hoskin DW, Easton AS. Bevacizumab diminishes experimental autoimmune encephalomyelitis by inhibiting spinal cord angiogenesis and reducing peripheral T-cell responses. J Neuropathol Exp Neurol 2012; 71(11):983–99.

24. Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O, Werb Z, et al. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 1999; 13(11): 1382–97.

25. Van Meir EG. Cytokines and tumors of the central nervous system. Glia 1995; 15(3):264–88.

26. Giovannoni G, Miller DH, Losseff NA, Sailer M, Lewellyn-Smith N, Thompson AJ, et al. Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis. J Neurol 2001;248(6):487–95.

27. Ziche M, Morbidelli L. Nitric oxide and angiogenesis. J Neurooncol 2000; 50(1-2):139–48.

28. Haufschild T, Shaw SG, Kesselring J, Flammer J.Increased endothelin-1 plasma levels in patients with multiple sclerosis. J Neuroophthalmol 2001; 21(1):37–8.

29. Shin T, Kang B, Tanuma N, Matsumoto Y, Wie M, Ahn M. et al. Intrathecal administration of endothelin-1 receptor antagonist ameliorates autoimmune encephalomyelitis in Lewis rats. Neuroreport 2001;12(7):1465–8.

30. Lu C, Pelech S, Zhang H, Bond J, Spach K, Noubade R, et al. Pertussis toxin induces angiogenesis in brain microvascular endothelial cells. J Neurosci Res 2008;86(12): 2624–40.

31. Kermode AG, Thompson AJ, Tofts P, MacManus DG, Kendall BE, Kingsley DP, et al. Breakdown of the blood– brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis Pathogenetic and clinical implications. Brain 1990; 113(Pt 5):1477–89.

32. Papadaki EZ, Simos PG, Mastorodemos VC, Panou T, Maris TG, Karantanas AH, et al. Regional MRI perfusion measures predict motor/ executive function in patients with Clinically Isolated Syndrome. Behav Neurol 2014;2014:252419.

33. Girolamo F, Coppola C, Ribatti D, Trojano M.Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathologica Communications 2014; 2:84.

34. Sasaki M, Lankford KL, Brown RJ, Ruddle NH, Kocsis JD. Focal experimental autoimmune encephalomyelitis in the Lewis rat induced by immunization with myelin oligodendrocyte glycoprotein and intraspinal injection of vascular endothelial growth factor. Glia 2010;58(13):1523–31.

35. Roscoe WA, Welsh ME, Carter DE, Karlik SJ. VEGF and angiogenesis in acute and chronic MOG (35–55) peptide induced EAE. J Neuroimmunol 2009; 209(1-2):6–15.

36. Proescholdt MA, Jacobson S, Tresser N, Oldfield EH, Merrill MJ. Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats. J Neuropathol Exp Neurol 2002;61(10):914–25.

37. Croll SD, Ransohoff RM, Cai N, Zhang Q, Martin FJ, Wei T, et al. VEGF mediated inflammation precedes angiogenesis in the adult brain. Exp Neurol 2004;187(2):388-402.

38. Semenza GL. Hydroxylation of HIF-1: Oxygen sensing at the molecular level. Physiology 2004; 19:176–82.

39. Semenza GL. Hypoxia-inducible factor 1: master regulator of O2 homeostasis. Curr Opin Genet Dev 1998;8(5):588–94.

40. Ben-Yosef Y, Miller A, Shapiro S, Lahat N. Hypoxia of endothelial cells leads to MMP-2-dependent survival and death. Am J Physiol Cell Physiol 2005;289(5):C1321-31.

41. Tang N, Wang L, Esko J, Giordano FJ, Huang Y, Gerber HP, et al. Loss of HIF-1alpha in endothelial cells disrupts a hypoxia driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell 2004; 6(5):485-95.

42. Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, et al. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 2005;9(5):617-28.

43. Sanchez-Elsner T, Botella LM, Velasco B, Corbi A, Attisano L, Bernabeu C. Synergistic cooperation between hypoxia and transforming growth factor pathways on human vascular endothelial growth factor gene expression. J Biol Chem 2001; 276(42):38527–35.

44. Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR. Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 1998; 21(2):75-80.

45. Grenier A, Chollet-Martin S, Crestani B, Delarche C, El Benna J, Boutten A, et al. Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils. Blood 2002; 99(8):2997–3004.

46. Muhs BE, Plitas G, Delgado Y, Ianus I, Shaw JP, Adelman MA, et al. Temporal expression and activation of matrix metalloproteinases-2, -9, and membrane type 1- matrix metalloproteinase following acute hind limb ischemia. J Surg Res 2003; 111(1):8–15.

47. Hoshino M, Takahashi M, Aoike N. Expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin immunoreactivity in asthmatic airways and its relationship to angiogenesis. J Allergy Clin Immunol 2001; 107(2):295–301.

48. de Paulis A, Prevete N, Rossi FW, Staibano S, Montuori N, Ragno P, et al. Expression and functions of vascular endothelial growth factors and their receptors in human basophils. J Immunol 2006; 177(10):7322–31.

49. Sörbo J, Jakobbson A, Norrby K. Mast cell histamine is angiogenic through receptors for histamine 1 and histamine 2. Int J Exp Pathol 1994; 75(1):43–50.

50. Naldini A, Carraro F. Role of inflammatory mediators in angiogenesis. Curr Drug Targets Inflamm Allergy 2005;4(1):3–8.

51. Noonan DM, De Lerma BA, Vannini N, Mortara L, Albini A. Inflammation, inflammatory cells and angiogenesis: decisions and indecisions. Cancer Metastasis Rev 2008; 27(1):31–40.

52. Jeon SH, Chae BC, Kim HA, Seo GY, Seo DW, Chun GT, et al. Mechanisms underlying TGF-beta 1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis. J Leukoc Biol 2007; 81(2):557-66.

53. Klimp AH, Hollema H, Kempinga C, van der Zee AGJ, de Vries EGE., Daemen, T. Expression of cyclooxygenase-2 and inducible nitric oxide synthase in human ovarian tumors and tumor-associated macrophages. Cancer Res 2001; 61(19):7305–9.

54. Jenkins DC, Charles IG, Thomsen LL, Moss DW, Holmes LS, Baylis SA, et al. Roles of nitric oxide in tumor growth. Proc Natl Acad Sci USA 1995;92(10):4392–6.

55. Gruber BL, Marchese MJ, Kew R. Angiogenic factors stimulate mast cell migration. Blood 1995; 86(7):2488–93.

56. Minagar A, Carpenter A, Alexander JS. The destructive alliance: Interactions of leukocytes, cerebral endothelial cells, and the immune cascade in pathogenesis of multiple sclerosis. Int Rev Neurobiol 2007; 79:1-11.

57. Mimura K, Kono K, Takahashi A, Kawaguchi Y, Fujii H.Vascular endothelial growth factor inhibits the function of human mature dendritic cells mediated by VEGF receptor-2. Cancer Immunol Immunother 2007;56(6):761–70.

58. Bourbié-Vaudanie S, Blanchard N, Hivroz C, Roméo P.Dendritic cells can turn CD4-T lymphocytes into vascular endothelial growth factor-carrying cells by intracellular neuropilin-1 transfer. J Immunol 2006; 177(3):1460–9.

59. Cannella B, Raine CS. The adhesion molecule and cytokine profile in MS lesions. Ann Neurol 1995;37(4):424–35.

60. Qutub AA, Mac Gabhann F, Karagiannis ED, Vempati P, Popel AS. Multiscale Models of Angiogenesis: Integration of Molecular Mechanisms with Cell- and Organ-Level Models IEEE. Eng Med Biol Mag 2009; 28(2):14–31.

61. Ferrara N. Vascular endothelial growth factor: basic sciences and clinical progress. Endocr Rev 2004;25(4):581– 611.

62. Frost EE, Nielsen JA, Le TQ, Armstrong RC. PDGF and FGF2 regulate oligodendrocyte progenitor responses to demyelination. J Neurobiol 2003; 54(3):457–72.

63. Harirchian MH, Tekieh AH, Modabbernia A, Aghamollaii V, Tafakhori A, Ghaffarpour M, et al. Serum and CSF PDGF-AA and FGF-2 in relapsing-remitting multiple sclerosis: a case-control study. Eur J Neurol 2012; 19(2):241-7.

64. Tham E, Gielen AW, Khademi M, Martin C, Piehl F.Decreased expression of VEGF-A in rat experimental autoimmune encephalomyelitis and in cerebro-spinal fluid mononuclear cells from patients with multiple sclerosis. Scand J Immunol 2006; 64(6):609-22.

65. Jackson JR, Seed MP, Kircher CH, Willoughby DA, Winkler JD. The Codependence of angiogenesis and chronic inflammation. FASEB J 1997; 11(6):457–65.

66. Krum JM, Mani N, Rosenstein JM. Roles of the endogenous VEGF receptors flt-1 and flk-1 in astroglial and vascular remodeling after brain injury. Exp Neurol 2008; 212(1):108–17.

67. Bouerat L, Fensholdt J, Liang X, Havez S, Nielsen SF, Hansen JR, et al. Indolin-2-ones with high in vivo efficacy in a model for multiple sclerosis. J Med Chem 2005; 48(17):5412–4.

68. Wei LH, Kuo ML, Chen CA, Chou CH, Lai KB, Lee CN, et al. Interleukin-6 promotes cervical tumor growth by VEGF-dependent angiogenesis via a STAT3 pathway. Oncogene 2003; 22(10):1517–27.

69. Su JJ, Osoegawa M, Matsuoka T, Minohara M, Tanaka M, Ishizu T, et al. Upregulation of vascular growth factors in multiple sclerosis: Correlation with MRI findings. J Neurol Sci 2006; 243(1-2):21–30.

70. Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, et al. Astrocyte-derived VEGF-A drives blood–brain barrier disruption in CNS inflammatory disease. J Clin Invest 2012; 122(7):2454–68.

71. Argaw AT, Gurfein BT, Zhang Y, Zameer A, John GR.VEGF mediated disruption of endothelial CLN-5 promotes blood–brain barrier breakdown. Proc Natl Acad Sci USA 2009; 106(6):1977–82.

72. Theoharides TC, Konstantinidou AD. Corticotropin- releasing hormone and the blood-brain-barrier. Front Biosci 2007; 12:1615–28.

73. Larochelle C, Alvarez JI, Prat A. How do immune cells overcome the blood–brain barrier in multiple sclerosis? FEBS Lett 2011; 585(23):3770–80.

74. Agrawal S, Anderson P, Durbeej M, van Rooijen N, Ivars F, Opdenakker G, et al. Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J Exp Med 2006; 203(4):1007–19.

75. Nygardas PT, Hinkkanen AE. Up-regulation of MMP-8 and MMP-9 activity in the BALB/c mouse spinal cord correlates with the severity of experimental autoimmune encephalomyelitis. Clin Exp Immunol 2002; 128(2):245–54.

76. Rosenberg GA, Yang Y. Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia. Neurosurg Focus 2007; 22(5):E4.

77. Agrawal SM, Lau L, Yong VW. MMPs in the central nervous system: where the good guys go bad. Semin Cell Dev Biol 2008; 19(1):42–51.

78. Bernal F, Elias B, Hartung HP, Kieseier BC. Regulation of matrix metalloproteinases and their inhibitors by interferon-beta: a longitudinal study in multiple sclerosis patients. Mult Scler 2009; 15(6):721–7.

79. Muroski ME, Roycik MD, Newcomer RG, Van den Steen PE, Opdenakker G, Monroe HR, et al. Matrix metalloproteinase-9/gelatinase B is a putative therapeutic target of chronic obstructive pulmonary disease and multiple sclerosis. Curr Pharm Biotechnol 2008; 9(1):34–46.

80. Zozulya AL, Reinke E, Baiu DC, Karman J, Sandor M, Fabry Z. Dendritic cell transmigration through brain microvessel endothelium is regulated by MIP-1alpha chemokine and matrix metalloproteinases. J Immunol 2007; 178(1):520–9.

81. Liu W, Hendren J, Qin XJ, Shen J, Liu KJ. Normobaric hyperoxia attenuates early blood–brain barrier disruption by inhibiting MMP-9-mediated occludin degradation in focal cerebral ischemia. J Neurochem 2009; 108(3):811–20.

82. Agrawal SM, Yong VW. The many faces of EMMPRIN – roles in neuroinflammation. Biochim Biophys Acta 2011; 1812(2):213–9.

83. Williams CS, DuBois RN. Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 1996; 270(3 Pt 1):G393–400.

84. Tanaka Y, Takahashi M, Kawaguchi M, Amano F.Delayed release of prostaglandins from arachidonic acid and kinetic changes in prostaglandin H synthase activity on the induction of prostaglandin H synthase-2 after lipopolysaccharide-treatment of RAW264.7 macrophage- like cells. Biol Pharm Bull 1997; 20(4):322–6.

85. Tsuji S, Kawano S, Tsujii M, Michida T, Masuda E, Gunawan ES, et al. Mucosal microcirculation and angiogenesis in gastrointestinal tract. Nippon Rinsho 1998; 56(9):2247–52.

86. Tsuji S, Tsujii M, Kawano S, Hori M. Cyclooxygenase-2 upregulation as a perigenetic change in carcinogenesis. J Exp Clin Cancer Res 2001; 20(1):117–29.

87. Kuwano T, Nakao S, Yamamoto H, Tsuneyoshi M, Yamamoto T, Kuwano M, et al. Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis. FASEB J 2004; 18(2):300–10.

88. Kirtikara K, Raghow R, Laulederkind SJ, Goorha S, Kanekura T, Ballou LR. Transcriptional regulation of cyclooxygenase-2 in the human microvascular endothelial cell line, HMEC-1: control by the combinatorial actions of AP2, NF-IL-6 and CRE elements. Mol Cell Biochem 2000; 203(1-2):41–51.

89. Caivano M, Cohen P. Role of mitogen-activated protein kinase cascades in mediating lipopolysaccharide- stimulated induction of cyclooxygenase-2 and IL-1 beta in RAW264 macrophages. J Immunol 2000;164(6):3018–25.

90. Salven P, Hattori K, Heissig B, Rafii S. Interleukin-1 promotes angiogenesis in vivo via VEGFR-2 pathway by inducing inflammatory cell VEGF synthesis and secretion. FASEB J 2002; 16(11):1471-3.

91. Argaw AT, Zhang Y, Snyder BJ, Zhao ML, Kopp N, Lee SC, et al. IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program. J Immunol 2006; 177(8):5574-84.

92. Laffon M, Pittet JF, Modelska K, Matthay MA, Young DM. Interleukin-8 mediates injury from smoke inhalation to both the lung endothelial and the alveolar epithelial barriers in rabbits. Am J Respir Crit Care Med 1999;160(5 Pt 1):1443–9.

93. Yao M, Zhou RH, Petreaca M, Zheng L, Shyy J, Martins- Green M. Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis. J Leukoc Biol 2006; 80(3):608–20.

94. Petreaca ML, Yao M, Liu Y, DeFea K, Martins-Green M.Transactivation of Vascular Endothelial Growth Factor Receptor-2 by Interleukin-8 (IL-8/CXCL8) Is Required for IL-8/CXCL8-induced Endothelial Permeability. Mol Biol Cell 2007; 18(12):5014–23.

95. Li A, Dubey S, Varney ML, Dave BJ, Singh RK. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol 2003; 170(6):3369–76.

96. Addison CL, Daniel TO, Burdick MD, Liu H, Ehlert JE, Xue YY, et al. The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR_ CXC chemokine-induced angiogenic activity. J Immunol 2000; 165(9):5269–77.

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IssueVol 15, No 1 (2016) QRcode
SectionReview Article(s)
Keywords
Angiogenesis inducing agent Blood-brain barrier Experimental autoimmune encephalomyelitis Endothelial cells Extracellular matrix Matrix metalloproteinase Multiple sclerosis Vascular endothelial growth factor A

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Hamid KM, Mirshafiey A. Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2016;15(1):1-12.