Current Allergy and Asthma Reports

, Volume 13, Issue 1, pp 1–9 | Cite as

Vascular Endothelial Growth Factor as a Key Inducer of Angiogenesis in the Asthmatic Airways

BASIC AND APPLIED SCIENCE (M FRIERI, SECTION EDITOR)

Abstract

Asthma is a chronic inflammatory disease of the airways characterized by structural airway changes, which are known as airway remodeling, including smooth muscle hypertrophy, goblet cell hyperplasia, subepithelial fibrosis, and angiogenesis. Vascular remodeling in asthmatic lungs results from increased angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF). VEGF is a key regulator of blood vessel growth in the airways of asthma patients by promoting proliferation and differentiation of endothelial cells and inducing vascular leakage and permeability. In addition, VEGF induces allergic inflammation, enhances allergic sensitization, and has a role in Th2 type inflammatory responses. Specific inhibitors of VEGF and blockers of its receptors might be useful to control chronic airway inflammation and vascular remodeling, and might be a new therapeutic approach for chronic inflammatory airway disease like asthma.

Keywords

Angiogenesis Asthma Vascular endothelial growth factor VEGF Interleukin-32 IL-32 Inflammatory pathways Airways Polymorphisms Novel therapies 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Dunnill MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960;13:27–33.PubMedCrossRefGoogle Scholar
  2. 2.
    Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438(7070):932–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Detoraki A, Granata F, Staibano S, et al. Angiogenesis and lymphangiogenesis in bronchial asthma. Allergy. 2010;65(8):946–58.PubMedCrossRefGoogle Scholar
  4. 4.
    Weis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med. 2011;17(11):1359–70.PubMedCrossRefGoogle Scholar
  5. 5.
    Liekens S, De Clercq E, Neyts J. Angiogenesis: regulators and clinical applications. Biochem Pharmacol. 2001;61(3):253–70.PubMedCrossRefGoogle Scholar
  6. 6.
    Zanini A, Chetta A, Imperatori AS, et al. The role of the bronchial microvasculature in the airway remodelling in asthma and COPD. Respir Res. 2010;11:132.PubMedCrossRefGoogle Scholar
  7. 7.
    Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219(4587):983–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Senger DR, Connolly DT, Van de Water L, et al. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res. 1990;50(6):1774–8.PubMedGoogle Scholar
  9. 9.
    Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9(6):669–76.PubMedCrossRefGoogle Scholar
  10. 10.
    Koch S, Tugues S, Li X, et al. Signal transduction by vascular endothelial growth factor receptors. Biochem J. 2011;437(2):169–83.PubMedCrossRefGoogle Scholar
  11. 11.
    Carmeliet P, Moons L, Luttun A, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001;7(5):575–83.PubMedCrossRefGoogle Scholar
  12. 12.
    Ziche M, Maglione D, Ribatti D, et al. Placenta growth factor-1 is chemotactic, mitogenic, and angiogenic. Lab Invest. 1997;76(4):517–31.PubMedGoogle Scholar
  13. 13.
    Luttun A, Tjwa M, Moons L, et al. Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med. 2002;8(8):831–40.PubMedGoogle Scholar
  14. 14.
    Frieri M. Asthma concepts in the new millennium: update in asthma pathophysiology. Allergy Asthma Proc. 2005;26(2):83–8.PubMedGoogle Scholar
  15. 15.
    Frieri M. Advances in the understanding of allergic asthma. Allergy Asthma Proc. 2007;28(6):614–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Kumar SD, Emery MJ, Atkins ND, et al. Airway mucosal blood flow in bronchial asthma. Am J Respir Crit Care Med. 1998;158(1):153–6.PubMedGoogle Scholar
  17. 17.
    Li X, Wilson JW. Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med. 1997;156(1):229–33.PubMedGoogle Scholar
  18. 18.
    Vrugt B, Wilson S, Bron A, et al. Bronchial angiogenesis in severe glucocorticoid-dependent asthma. Eur Respir J. 2000;15(6):1014–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Barbato A, Turato G, Baraldo S, et al. Epithelial damage and angiogenesis in the airways of children with asthma. Am J Respir Crit Care Med. 2006;174(9):975–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Tigani B, Cannet C, Karmouty-Quintana H, et al. Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI. Am J Physiol Lung Cell Mol Physiol. 2007;292(3):L644–53.PubMedCrossRefGoogle Scholar
  21. 21.
    Rydell-Tormanen K, Johnson JR, Fattouh R, et al. Induction of vascular remodeling in the lung by chronic house dust mite exposure. Am J Respir Cell Mol Biol. 2008;39(1):61–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Tormanen KR, Uller L, Persson CG, et al. Allergen exposure of mouse airways evokes remodeling of both bronchi and large pulmonary vessels. Am J Respir Crit Care Med. 2005;171(1):19–25.PubMedCrossRefGoogle Scholar
  23. 23.
    Capetandes A, Horne NS, Frieri M. Dermatophagoides extract-treated confluent type II epithelial cells (cA549) and human lung mesenchymal cell growth. Ann Allergy Asthma Immunol. 2005;95(4):381–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Frieri M, Capetandes A. The effect of enantiomers of beta-agonists on myofibroblast-derived vascular endothelial growth factor and other matrix components in the presence of dust-mite extract. Allergy Asthma Proc. 2008;29(2):182–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Hoshino M, Nakamura Y, Hamid QA. Gene expression of vascular endothelial growth factor and its receptors and angiogenesis in bronchial asthma. J Allergy Clin Immunol. 2001;107(6):1034–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Asai K, Kanazawa H, Kamoi H, et al. Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients. Clin Exp Allergy. 2003;33(5):595–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Siddiqui S, Sutcliffe A, Shikotra A, et al. Vascular remodeling is a feature of asthma and nonasthmatic eosinophilic bronchitis. J Allergy Clin Immunol. 2007;120(4):813–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Abdel-Rahman AM, el-Sahrigy SA, Bakr SI. A comparative study of two angiogenic factors: vascular endothelial growth factor and angiogenin in induced sputum from asthmatic children in acute attack. Chest. 2006;129(2):266–71.PubMedCrossRefGoogle Scholar
  29. 29.
    Mura M, dos Santos CC, Stewart D, et al. Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol. 2004;97(5):1605–17.PubMedCrossRefGoogle Scholar
  30. 30.•
    Lopez-Guisa JM, Powers C, File D, et al. Airway epithelial cells from asthmatic children differentially express proremodeling factors. J Allergy Clin Immunol;129(4):990–7 e6. The authors demonstrate that VEGF production is significantly greater in bronchial and nasal air−liquid interface cultures from asthmatic children than in cultures from atopic non-asthmatic and healthy children. Google Scholar
  31. 31.
    Simcock DE, Kanabar V, Clarke GW, et al. Induction of angiogenesis by airway smooth muscle from patients with asthma. Am J Respir Crit Care Med. 2008;178(5):460–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Clifford RL, John AE, Brightling CE, et al. Abnormal histone methylation is responsible for increased vascular endothelial growth factor 165a secretion from airway smooth muscle cells in asthma. J Immunol. 2012;189(2):819–31.PubMedCrossRefGoogle Scholar
  33. 33.
    Fujita H, Chalubinski M, Rhyner C, et al. Claudin-1 expression in airway smooth muscle exacerbates airway remodeling in asthmatic subjects. J Allergy Clin Immunol. 2011;127(6):1612–21. e8.PubMedCrossRefGoogle Scholar
  34. 34.
    Wang H, Keiser JA. Vascular endothelial growth factor upregulates the expression of matrix metalloproteinases in vascular smooth muscle cells: role of flt-1. Circ Res. 1998;83(8):832–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Lee KS, Min KH, Kim SR, et al. Vascular endothelial growth factor modulates matrix metalloproteinase-9 expression in asthma. Am J Respir Crit Care Med. 2006;174(2):161–70.PubMedCrossRefGoogle Scholar
  36. 36.
    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.PubMedCrossRefGoogle Scholar
  37. 37.
    de Paulis A, Prevete N, Fiorentino I, et al. Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. J Immunol. 2006;177(10):7322–31.PubMedGoogle Scholar
  38. 38.
    Sumbayev VV, Nicholas SA, Streatfield CL, et al. Involvement of hypoxia-inducible factor-1 HiF(1alpha) in IgE-mediated primary human basophil responses. Eur J Immunol. 2009;39(12):3511–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Chetta A, Zanini A, Foresi A, et al. Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma. Clin Exp Allergy. 2005;35(11):1437–42.PubMedCrossRefGoogle Scholar
  40. 40.
    Zanini A, Chetta A, Saetta M, et al. Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma. J Allergy Clin Immunol. 2007;120(2):329–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Sismanopoulos N, Delivanis DA, Alysandratos KD, et al. IL-9 induces VEGF secretion from human mast cells and IL-9/IL-9 receptor genes are overexpressed in atopic dermatitis. PLoS One. 2012;7(3):e33271.PubMedCrossRefGoogle Scholar
  42. 42.
    Poulin S, Thompson C, Thivierge M, et al. Cysteinyl-leukotrienes induce vascular endothelial growth factor production in human monocytes and bronchial smooth muscle cells. Clin Exp Allergy. 2010;41(2):204–17.PubMedCrossRefGoogle Scholar
  43. 43.
    Wen FQ, Liu X, Manda W, et al. TH2 Cytokine-enhanced and TGF-beta-enhanced vascular endothelial growth factor production by cultured human airway smooth muscle cells is attenuated by IFN-gamma and corticosteroids. J Allergy Clin Immunol. 2003;111(6):1307–18.PubMedCrossRefGoogle Scholar
  44. 44.
    Lee CG, Link H, Baluk P, et al. Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nat Med. 2004;10(10):1095–103.PubMedCrossRefGoogle Scholar
  45. 45.
    Calhoun WJ, Dick EC, Schwartz LB, et al. A common cold virus, rhinovirus 16, potentiates airway inflammation after segmental antigen bronchoprovocation in allergic subjects. J Clin Invest. 1994;94(6):2200–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Bufe A, Gehlhar K, Grage-Griebenow E, et al. Atopic phenotype in children is associated with decreased virus-induced interferon-alpha release. Int Arch Allergy Immunol. 2002;127(1):82–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Gehlhar K, Bilitewski C, Reinitz-Rademacher K, et al. Impaired virus-induced interferon-alpha2 release in adult asthmatic patients. Clin Exp Allergy. 2006;36(3):331–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Pritchard AL, Carroll ML, Burel JG, et al. Innate IFNs and Plasmacytoid Dendritic Cells Constrain Th2 Cytokine Responses to Rhinovirus: A Regulatory Mechanism with Relevance to Asthma. J Immunol. 2012;188(12):5898–905.PubMedCrossRefGoogle Scholar
  49. 49.
    Psarras S, Volonaki E, Skevaki CL, et al. Vascular endothelial growth factor-mediated induction of angiogenesis by human rhinoviruses. J Allergy Clin Immunol. 2006;117(2):291–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Meyer N, Christoph J, Makrinioti H, et al. Inhibition of angiogenesis by IL-32: possible role in asthma. J Allergy Clin Immunol. 2012;129(4):964–73. e7.PubMedCrossRefGoogle Scholar
  51. 51.
    Soyka MB, Treis A, Eiwegger T, et al. Regulation and expression of IL-32 in chronic rhinosinusitis. Allergy. 2012;67(6):790–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Nold-Petry CA, Nold MF, Zepp JA, et al. IL-32-dependent effects of IL-1beta on endothelial cell functions. Proc Natl Acad Sci U S A. 2009;106(10):3883–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Meyer N, Zimmermann M, Burgler S, et al. IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis. J Allergy Clin Immunol. 2010;125(4):858–65. e10.PubMedCrossRefGoogle Scholar
  54. 54.
    Fort MM, Cheung J, Yen D, et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2001;15(6):985–95.PubMedCrossRefGoogle Scholar
  55. 55.
    Tamachi T, Maezawa Y, Ikeda K, et al. IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice. J Allergy Clin Immunol. 2006;118(3):606–14.PubMedCrossRefGoogle Scholar
  56. 56.
    Petersen BC, Budelsky AL, Baptist AP, et al. Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB + myeloid population that exacerbates asthmatic pathology. Nat Med. 2012;18(5):751–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Corrigan CJ, Wang W, Meng Q, et al. T-helper cell type 2 (Th2) memory T cell-potentiating cytokine IL-25 has the potential to promote angiogenesis in asthma. Proc Natl Acad Sci U S A. 2011;108(4):1579–84.PubMedCrossRefGoogle Scholar
  58. 58.
    Palmer MT, Weaver CT. Autoimmunity: increasing suspects in the CD4+ T cell lineup. Nat Immunol. 2009;11(1):36–40.PubMedCrossRefGoogle Scholar
  59. 59.
    Maniati E, Soper R, Hagemann T. Up for Mischief? IL-17/Th17 in the tumour microenvironment. Oncogene;29(42):5653–62.Google Scholar
  60. 60.
    Kudo M, Melton AC, Chen C, et al. IL-17A produced by alphabeta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med. 2012;18(4):547–54.PubMedCrossRefGoogle Scholar
  61. 61.
    Akdis M, Palomares O, van de Veen W, et al. TH17 and TH22 cells: a confusion of antimicrobial response with tissue inflammation versus protection. J Allergy Clin Immunol. 2012;129(6):1438–49. quiz1450-1.PubMedCrossRefGoogle Scholar
  62. 62.
    Numasaki M, Lotze MT, Sasaki H. Interleukin-17 augments tumor necrosis factor-alpha-induced elaboration of proangiogenic factors from fibroblasts. Immunol Lett. 2004;93(1):39–43.PubMedCrossRefGoogle Scholar
  63. 63.
    Chauhan SK, Jin Y, Goyal S, et al. A novel pro-lymphangiogenic function for Th17/IL-17. Blood. 2011;118(17):4630–4.PubMedCrossRefGoogle Scholar
  64. 64.
    Hahn RG. Endotoxin boosts the vascular endothelial growth factor (VEGF) in rabbits. J Endotoxin Res. 2003;9(2):97–100.PubMedGoogle Scholar
  65. 65.
    Kim YS, Hong SW, Choi JP, et al. Vascular endothelial growth factor is a key mediator in the development of T cell priming and its polarization to type 1 and type 17 T helper cells in the airways. J Immunol. 2009;183(8):5113–20.PubMedCrossRefGoogle Scholar
  66. 66.
    Choi JP, Kim YS, Tae YM, et al. A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6. Allergy. 2010;65(10):1322–30.PubMedCrossRefGoogle Scholar
  67. 67.
    Bilton RL, Booker GW. The subtle side to hypoxia inducible factor (HIFalpha) regulation. Eur J Biochem. 2003;270(5):791–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Semenza GL. Expression of hypoxia-inducible factor 1: mechanisms and consequences. Biochem Pharmacol. 2000;59(1):47–53.PubMedCrossRefGoogle Scholar
  69. 69.
    Kim SR, Lee KS, Park HS, et al. HIF-1alpha inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium. Eur J Immunol. 2010;40(10):2858–69.PubMedCrossRefGoogle Scholar
  70. 70.
    Lee YC, Jogie-Brahim S, Lee DY, et al. Insulin-like growth factor-binding protein-3 (IGFBP-3) blocks the effects of asthma by negatively regulating NF-kappaB signaling through IGFBP-3R-mediated activation of caspases. J Biol Chem. 2011;286(20):17898–909.PubMedCrossRefGoogle Scholar
  71. 71.
    Kim SR, Lee KS, Lee KB, et al. Recombinant IGFBP-3 inhibits allergic lung inflammation, VEGF production, and vascular leak in a mouse model of asthma. Allergy. 2012;67(7):869–77.PubMedCrossRefGoogle Scholar
  72. 72.
    Huerta-Yepez S, Baay-Guzman GJ, Bebenek IG, et al. Hypoxia inducible factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis. Allergy. 2011;66(7):909–18.PubMedCrossRefGoogle Scholar
  73. 73.
    Sharma S, Murphy AJ, Soto-Quiros ME, et al. Association of VEGF polymorphisms with childhood asthma, lung function and airway responsiveness. Eur Respir J. 2009;33(6):1287–94.PubMedCrossRefGoogle Scholar
  74. 74.
    Simpson A, Custovic A, Tepper R, et al. Genetic variation in vascular endothelial growth factor-a and lung function. Am J Respir Crit Care Med;185(11):1197–204.Google Scholar
  75. 75.
    Balantic M, Rijavec M, Skerbinjek Kavalar M, et al. Asthma Treatment Outcome in Children Is Associated with Vascular Endothelial Growth Factor A (VEGFA) Polymorphisms. Mol Diagn Ther. 2012;16(3):173–80.PubMedCrossRefGoogle Scholar
  76. 76.
    Simpson A, Custovic A, Tepper R, et al. Genetic variation in vascular endothelial growth factor-a and lung function. Am J Respir Crit Care Med. 2012;185(11):1197–204.PubMedCrossRefGoogle Scholar
  77. 77.
    Li J, Huang J, Dai L, et al. miR-146a, an IL-1beta responsive miRNA, induces vascular endothelial growth factor and chondrocyte apoptosis by targeting Smad4. Arthritis Res Ther. 2012;14(2):R75.PubMedCrossRefGoogle Scholar
  78. 78.
    Chen Y, Gorski DH. Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood. 2008;111(3):1217–26.PubMedCrossRefGoogle Scholar
  79. 79.
    Anand S, Majeti BK, Acevedo LM, et al. MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med. 2010;16(8):909–14.PubMedCrossRefGoogle Scholar
  80. 80.
    Liu B, Peng XC, Zheng XL, et al. MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer. 2009;66(2):169–75.PubMedCrossRefGoogle Scholar
  81. 81.
    Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15(2):272–84.PubMedCrossRefGoogle Scholar
  82. 82.
    Song C, Ma H, Yao C, et al. Alveolar macrophage-derived vascular endothelial growth factor contributes to allergic airway inflammation in a mouse asthma model. Scand J Immunol. 2012;75(6):599–605.PubMedCrossRefGoogle Scholar
  83. 83.
    Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008;31(1):143–78.PubMedCrossRefGoogle Scholar
  84. 84.
    Hoshino M, Takahashi M, Takai Y, et al. Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma. Clin Exp Allergy. 2001;31(5):722–30.PubMedCrossRefGoogle Scholar
  85. 85.
    Chetta A, Zanini A, Foresi A, et al. Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone. Am J Respir Crit Care Med. 2003;167(5):751–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Wang K, Liu CT, Wu YH, et al. Budesonide/formoterol decreases expression of vascular endothelial growth factor (VEGF) and VEGF receptor 1 within airway remodelling in asthma. Adv Ther. 2008;25(4):342–54.PubMedCrossRefGoogle Scholar
  87. 87.
    Feltis BN, Wignarajah D, Reid DW, et al. Effects of inhaled fluticasone on angiogenesis and vascular endothelial growth factor in asthma. Thorax. 2007;62(4):314–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Akdis CA. Therapies for allergic inflammation: refining strategies to induce tolerance. Nat Med. 2012;18(5):736–49.PubMedCrossRefGoogle Scholar
  89. 89.
    Dupont E, Savard PE, Jourdain C, et al. Antiangiogenic properties of a novel shark cartilage extract: potential role in the treatment of psoriasis. J Cutan Med Surg. 1998;2(3):146–52.PubMedGoogle Scholar
  90. 90.
    Lee SY, Paik SY, Chung SM. Neovastat (AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma. J Microbiol. 2005;43(1):11–6.PubMedGoogle Scholar
  91. 91.
    Lee SY, Chung SM. Neovastat (AE-941) inhibits the airway inflammation via VEGF and HIF-2 alpha suppression. Vascul Pharmacol. 2007;47(5–6):313–8.PubMedCrossRefGoogle Scholar
  92. 92.
    He K, Cui B, Li G, et al. The effect of anti-VEGF drugs (bevacizumab and aflibercept) on the survival of patients with metastatic colorectal cancer (mCRC). Onco Targets Ther. 2012;5:59–65.PubMedGoogle Scholar
  93. 93.
    Michels S, Rosenfeld PJ, Puliafito CA, et al. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve-week results of an uncontrolled open-label clinical study. Ophthalmology. 2005;112(6):1035–47.PubMedCrossRefGoogle Scholar
  94. 94.
    Lee YC, Kwak YG, Song CH. Contribution of vascular endothelial growth factor to airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma. J Immunol. 2002;168(7):3595–600.PubMedGoogle Scholar
  95. 95.
    Kim SR, Lee KS, Park SJ, et al. Inhibition of p38 MAPK reduces expression of vascular endothelial growth factor in allergic airway disease. J Clin Immunol. 2012;32(3):574–86.PubMedCrossRefGoogle Scholar
  96. 96.
    Powers KW, Brown SC, Krishna VB, et al. Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation. Toxicol Sci. 2006;90(2):296–303.PubMedCrossRefGoogle Scholar
  97. 97.
    Tsuji JS, Maynard AD, Howard PC, et al. Research strategies for safety evaluation of nanomaterials, part IV: risk assessment of nanoparticles. Toxicol Sci. 2006;89(1):42–50.PubMedCrossRefGoogle Scholar
  98. 98.
    Syed S, Zubair A, Frieri M. Immune Response to Nanomaterials: Implications for Medicine and Literature Review. Curr Allergy Asthma Rep.Google Scholar
  99. 99.
    Kalishwaralal K, Banumathi E, Ram Kumar Pandian S, et al. Silver nanoparticles inhibit VEGF induced cell proliferation and migration in bovine retinal endothelial cells. Colloids Surf B Biointerfaces. 2009;73(1):51–7.PubMedCrossRefGoogle Scholar
  100. 100.•
    Jang S, Park JW, Cha HR, et al. Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation. Int J Nanomedicine. 2012;7:1329–43. The authors demonstrate that silver nanoparticles substantially suppressed mucus hypersecretion and the PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.PubMedGoogle Scholar
  101. 101.
    Scarino A, Noel A, Renzi PM, et al. Impact of emerging pollutants on pulmonary inflammation in asthmatic rats: ethanol vapors and agglomerated TiO(2) nanoparticles. Inhal Toxicol. 2012;24(8):528–38.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Swiss Institute of Allergy and Asthma Research (SIAF)University of Zurich, Christine Kühne Center for Allergy Research and Education (CK-CARE)DavosSwitzerland
  2. 2.Spitalnetz Bern, Ziegler Hospital Department of Internal MedicineBernSwitzerland
  3. 3.Spital ZieglerBernSwitzerland

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