Skip to main content

Advertisement

SpringerLink
Log in

Angiogenesis and Vascular Remodeling in Chronic Airway Diseases

  • Review Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Asthma and chronic obstructive pulmonary disease remain a global health problem, with increasing morbidity and mortality. Despite differences in the causal agents, both diseases exhibit various degrees of inflammatory changes, structural alterations of the airways leading to airflow limitation. The existence of transient disease phenotypes which overlap both diseases and which progressively decline the lung function has complicated the search for an effective therapy. Important characteristics of chronic airway diseases include airway and vascular remodeling, of which the molecular mechanisms are complex and poorly understood. Recently, we and others have shown that airway smooth muscle (ASM) cells are not only structural and contractile components of airways, rather they bear capabilities of producing large number of pro-inflammatory and mitogenic factors. Increase in size and number of blood vessels both inside and outside the smooth muscle layer as well as hyperemia of bronchial vasculature are contributing factors in airway wall remodeling in patients with chronic airway diseases, proposing for the ongoing mechanisms like angiogenesis and vascular dilatation. We believe that vascular changes directly add to the airway narrowing and hyper-responsiveness by exudation and transudation of proinflammatory mediators, cytokines and growth factors; facilitating trafficking of inflammatory cells; causing oedema of the airway wall and promoting ASM accumulation. One of the key regulators of angiogenesis, vascular endothelial growth factor in concerted action with other endothelial mitogens play pivotal role in regulating bronchial angiogenesis. In this review article we address recent advances in pulmonary angiogenesis and remodelling that contribute in the pathogenesis of chronic airway diseases.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. World Health Organization. (2010). Diseases of the respiratory system. In International Statistical Classification of Diseases and Related Health Problems (ICD-10). Chapter X. http://www.who.int/classifications/icd/en/. Accessed 18 July 2013.

  2. Celli, B. R., & MacNee, W. (2004). Standards for the diagnosis and treatment of patients with COPD: A summary of the ATS/ERS position paper. European Respiratory Journal, 23, 932–946.

    Article  PubMed  CAS  Google Scholar 

  3. Hogg, J. C. (2004). Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet, 364, 709–721.

    Article  PubMed  Google Scholar 

  4. Aoshiba, K., & Nagai, A. (2004). Differences in airway remodeling between asthma and chronic obstructive pulmonary disease. Clinical Reviews in Allergy and Immunology, 27, 35–43.

    Article  PubMed  CAS  Google Scholar 

  5. Global Initiative for Chronic Obstructive Lung Disease (GOLD). (2013). In Global Strategy for the Diagnosis, Management and Prevention of COPD. http://www.goldcopd.org/. Accessed 18 July 2013.

  6. Rutgers, S. R., Timens, W., Kauffman, H. F., & Postma, D. S. (2001). Markers of active airway inflammation and remodelling in chronic obstructive pulmonary disease. Clinical and Experimental Allergy, 31, 193–205.

    Article  PubMed  CAS  Google Scholar 

  7. Rabe, K. F., Hurd, S., Anzueto, A., et al. (2007). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. American Journal of Respiratory and Critical Care Medicine, 176, 532–555.

    Article  PubMed  Google Scholar 

  8. Barnes, P. J., Shapiro, S. D., & Pauwels, R. A. (2003). Chronic obstructive pulmonary disease: Molecular and cellular mechanisms. European Respiratory Journal, 22, 672–688.

    Article  PubMed  CAS  Google Scholar 

  9. Hogg, J. C., & Timens, W. (2009). The pathology of chronic obstructive pulmonary disease. Annual Review of Pathology: Mechanisms of Disease, 4, 435–459.

    Article  CAS  Google Scholar 

  10. McDonough, J. E., Yuan, R., Suzuki, M., Seyednejad, N., Elliott, W. M., Sanchez, P. G., et al. (2011). Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. New England Journal of Medicine, 365(17), 1567–1575.

    Article  PubMed  CAS  Google Scholar 

  11. Jeffery, P. K. (2004). Remodeling and inflammation of bronchi in asthma and chronic obstructive pulmonary disease. Proceedings of the American Thoracic Society, 1, 176–183.

    Article  PubMed  CAS  Google Scholar 

  12. Sohal, S. S., Ward, C., Danial, W., Wood-Baker, R., & Walters, E. H. (2013). Recent advances in understanding inflammation and remodeling in the airways in chronic obstructive pulmonary disease. Expert Review of Respiratory Medicine, 7(3), 275–288.

    Article  PubMed  CAS  Google Scholar 

  13. McKay, S., & Sharma, H. S. (2002). Autocrine regulation of asthmatic airway inflammation: Role of airway smooth muscle. Respiratory Research, 3(11), p1–p13.

    Google Scholar 

  14. Global Strategy for Asthma Management and Prevention. (2012). In Global Initiative for Asthma (GINA). http://www.ginasthma.org/. Accessed 18 July 2013.

  15. Manuyakorn, W., Howarth, P. H., & Holgate, S. T. (2013). Airway remodelling in asthma and novel therapy. Asian Pacific Journal of Allergy and Immunology, 31(1), 3–10.

    PubMed  CAS  Google Scholar 

  16. Barnes, P. J. (2012). New drugs for asthma. Seminars in Respiratory and Critical Care Medicine, 3(6), 685–694.

    Google Scholar 

  17. Hislop, A. A. (2002). Airway and blood vessel interaction during lung development. Journal of Anatomy, 201, 325–334.

    Article  PubMed  Google Scholar 

  18. Cardoso, W. V. (2001). Molecular regulation of lung development. Annual Review of Physiology, 63, 471–494.

    Article  PubMed  CAS  Google Scholar 

  19. Mitzner, W., & Wagner, E. M. (2004). Vascular remodeling in the circulations of the lung. Journal of Applied Physiology, 97, 1999–2004.

    Article  PubMed  Google Scholar 

  20. McDonald, D. M. (1990). The ultrastructure and permeability of tracheobronchial blood vessels in health and disease. European Respiratory Journal Supplement, 12, 572s–585s.

    CAS  Google Scholar 

  21. Lakshminarayan, S., Bernard, S., Polissar, N. L., & Glenny, R. W. (1999). Pulmonary and bronchial circulatory responses to segmental lung injury. Journal of Applied Physiology, 87, 1931–1936.

    PubMed  CAS  Google Scholar 

  22. Wagner, E. M., & Mitzner, W. A. (1988). Effect of hypoxia on bronchial circulation. Journal of Applied Physiology, 65, 1627–1633.

    PubMed  CAS  Google Scholar 

  23. Kranenburg, A. R., De Boer, W. I., Van Krieken, J. H., Mooi, W. J., Walters, J. E., Saxena, P. R., et al. (2002). Enhanced expression of fibroblast growth factors and receptor FGFR-1 during vascular remodeling in chronic obstructive pulmonary disease. American Journal of Respiratory Cell and Molecular Biology, 27, 517–525.

    Article  PubMed  CAS  Google Scholar 

  24. Peinado, V. I., Barbera, J. A., Abate, P., Ramirez, J., Roca, J., Santos, S., et al. (1999). Inflammatory reaction in pulmonary muscular arteries of patients with mild chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 159, 1605–1611.

    Article  PubMed  CAS  Google Scholar 

  25. Santos, S., Peinado, V. I., Ramirez, J., Melgosa, T., Roca Rodriguez-Roisin, R., & Barberà, J. A. (2002). Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. European Respiratory Journal, 19, 632–638.

    Article  PubMed  CAS  Google Scholar 

  26. Chetta, A., Zanini, A., Foresi, A., Del Donno, M., Castagnaro, A., & D’Ippolito, R. (2003). Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone. American Journal of Respiratory and Critical Care Medicine, 167, 751–757.

    Article  PubMed  Google Scholar 

  27. Meyer, N., & Akdis, C. A. (2013). Vascular endothelial growth factor as a key inducer of angiogenesis in the asthmatic airways. Current Allergy and Asthma Reports, 13(1), 1–9.

    Article  PubMed  CAS  Google Scholar 

  28. Van der Velden, J., Barker, D., Barcham, G., Koumoundouros, E., & Snibson, K. (2012). Increased vascular density is a persistent feature of airway remodeling in a sheep model of chronic asthma. Experimental Lung Research, 38(6), 307–315.

    Article  PubMed  Google Scholar 

  29. Salvato, G. (2001). Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects. Thorax, 56, 902–906.

    Article  PubMed  CAS  Google Scholar 

  30. Wilson, J. W., & Li, X. (2001). Vessels: New targets for asthma treatment. Thorax, 6, 899–900.

    Article  Google Scholar 

  31. Hashimoto, M., Tanaka, H., & Abe, S. (2005). Quantitative analysis of bronchial wall vascularity in the medium and small airways of patients with asthma and COPD. Chest, 200127, 965–972.

    Article  Google Scholar 

  32. McDonald, D. M. (2001). Angiogenesis and remodeling of airway vasculature in chronic inflammation. American Journal of Respiratory and Critical Care Medicine, 164, S39–S45.

    Article  PubMed  CAS  Google Scholar 

  33. Carroll, N. G., Cooke, C., & James, A. L. (1997). Bronchial blood vessel dimensions in asthma. American Journal of Respiratory and Critical Care Medicine, 155, 689–695.

    Article  PubMed  CAS  Google Scholar 

  34. Kranenburg, A. R., de Boer, W. I., Alagappan, V. K., Sterk, P. J., & Sharma, H. S. (2005). Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease. Thorax, 60, 106–113.

    Article  PubMed  CAS  Google Scholar 

  35. Wright, J. L., Petty, T., & Thurlbeck, W. M. (1992). Analysis of the structure of the muscular pulmonary arteries in patients with pulmonary hypertension and COPD: National Institutes of Health nocturnal oxygen therapy trial. Lung, 170, 109–124.

    Article  PubMed  CAS  Google Scholar 

  36. Bailey, S. R., Boustany, S., Burgess, J. K., Hirst, S. J., Sharma, H. S., Simcock, D. E., et al. (2009). Airway vascular reactivity and vascularisation in human chronic airway disease. Pulmonary Pharmacology and Therapeutics, 22(5), 417–425.

    Article  PubMed  CAS  Google Scholar 

  37. Zanini, A., Chetta, A., Imperatori, A. S., Spanevello, A., & Olivieri, D. (2010). The role of the bronchial microvasculature in the airway remodelling in asthma and COPD. Respiratory Research, 11, 132.

    Article  PubMed  CAS  Google Scholar 

  38. Detoraki, A., Granata, F., Staibano, S., Rossi, F. W., Marone, G., & Genovese, A. (2010). Angiogenesis and lymphangiogenesis in bronchial asthma. Allergy, 65(8), 946–958.

    Article  PubMed  CAS  Google Scholar 

  39. Paredi, P., & Barnes, P. J. (2009). The airway vasculature: Recent advances and clinical implications. Thorax, 64(5), 444–450.

    Article  PubMed  CAS  Google Scholar 

  40. Deindl, E., & Schaper, W. (2005). The art of arteriogenesis. Cell Biochemistry and Biophysics, 43(1), 1–15.

    Article  PubMed  CAS  Google Scholar 

  41. Carmeliet, P. (2000). Mechanisms of angiogenesis and arteriogenesis. Nature Medicine, 6(4), 389–395.

    Article  PubMed  CAS  Google Scholar 

  42. Zanini, A., Chetta, A., & Olivieri, D. (2008). Therapeutic perspectives in bronchial vascular remodeling in COPD. Therapeutic Advances in Respiratory Disease, 2(3), 179–187.

    Article  PubMed  Google Scholar 

  43. Ribatti, D., Puxeddu, I., Crivellato, E., Nico, B., Vacca, A., & Levi-Schaffer, F. (2009). Angiogenesis in asthma. Clinical and Experimental Allergy, 39(12), 1815–1821.

    Article  PubMed  CAS  Google Scholar 

  44. Peinado, V. I., Barbera, J. A., Ramirez, J., Gomez, F. P., Roca, J., Jover, L., et al. (1998). Endothelial dysfunction in pulmonary arteries of patients with mild COPD. American Journal of Physiology, 274, L908–L913.

    PubMed  CAS  Google Scholar 

  45. Kasahara, Y., Tuder, R. M., Cool, C. D., Lynch, D. A., Flores, S. C., & Voelkel, N. F. (2001). Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. American Journal of Respiratory and Critical Care Medicine, 163(3 Pt 1), 737–744.

    Article  PubMed  CAS  Google Scholar 

  46. Magee, F., Wright, J. L., Wiggs, B. R., Pare, P. D., & Hogg, J. C. (1988). Pulmonary vascular structure and function in chronic obstructive pulmonary disease. Thorax, 43, 183–189.

    Article  PubMed  CAS  Google Scholar 

  47. Frid, M. G., Kale, V. A., & Stenmark, K. R. (2002). Mature vascular endothelium can give rise to smooth muscle cells via endothelial-mesenchymal transdifferentiation: In vitro analysis. Circulation Research, 90, 1189–1196.

    Article  PubMed  CAS  Google Scholar 

  48. Díez, M., Barberà, J. A., Ferrer, E., Fernández-Lloris, R., Pizarro, S., Roca, J., et al. (2007). Plasticity of CD133+ cells: Role in pulmonary vascular remodeling. Cardiovascular Research, 76, 517–527.

    Article  PubMed  CAS  Google Scholar 

  49. Rahman, I., van Schadewijk, A. A., Crowther, A. J., Hiemstra, P. S., Stolk, J., MacNee, W., et al. (2002). 4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 166, 490–495.

    Article  PubMed  Google Scholar 

  50. Parameswaran, K., Widyastuti, A. W., Alagappan, V. K. T., Radford, K., Kranenburg, A. R., & Sharma, H. S. (2006). Role of extracellular matrix and its regulators in human airway smooth muscle biology. Cell Biochemistry and Biophysics, 44, 139–146.

    Article  PubMed  CAS  Google Scholar 

  51. Kranenburg, A. R., Willems-Widyastuti, A., Moori, W. J., Sterk, P. J., Alagappan, V. K., de Boer, W. I., et al. (2006). Enhanced bronchial expression of extracellular matrix proteins in chronic obstructive pulmonary disease. American Journal of Clinical Pathology, 126(5), 725–735.

    Article  PubMed  CAS  Google Scholar 

  52. Walters, E. H., Reid, D., Soltani, A., & Ward, C. (2008). Angiogenesis: A potentially critical part of remodelling in chronic airway diseases? Pharmacology and Therapeutics, 118(1), 128–137.

    Article  PubMed  CAS  Google Scholar 

  53. Somanath, P. R., Ciocea, A., & Byzova, T. V. (2009). Integrin and growth factor receptor alliance in angiogenesis. Cell Biochemistry and Biophysics, 53, 53–64.

    Article  PubMed  CAS  Google Scholar 

  54. Takeyama, K., Jung, B., Shim, J. J., Burgel, P. R., Dao-Pick, T., Ueki, I. F., et al. (2001). Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. American Journal of Physiology. Lung Cellular and Molecular Physiology, 280, L165–L172.

    PubMed  CAS  Google Scholar 

  55. Ganesan, S., Unger, B. L., Comstock, A. T., Angel, K. A., Mancuso, P., Martinez, F. J., et al. (2013). Aberrantly activated EGFR contributes to enhanced IL-8 expression in COPD airways epithelial cells via regulation of nuclear FoxO3A. Thorax, 68(2), 131–141.

    Article  PubMed  Google Scholar 

  56. Polosa, R., Puddicombe, S. M., Krishna, M. T., Tuck, A. B., Howarth, P. H., & Holgate, S. T. (2002). Expression of c-erbB receptors and ligands in the bronchial epithelium of asthmatic subjects. Journal of Allergy and Clinical Immunology, 109, 75–81.

    Article  PubMed  CAS  Google Scholar 

  57. de Boer, W. I., Hau, C. M., Schadewijk, A., Stolk, J., Krieken, J. H., & Hiemstra, P. S. (2006). Expression of epidermal growth factors and their receptors in the bronchial epithelium of subjects with chronic obstructive pulmonary disease. American Journal of Clinical Pathology, 125, 1–9.

    Google Scholar 

  58. Sproul, E. P., & Argraves, W. S. (2013). A cytokine axis regulates elastin formation and degradation. Matrix Biology, 32, 86–94.

    Article  PubMed  CAS  Google Scholar 

  59. DiCamillo, S. J., Yang, S., Panchenko, M. V., Toselli, P. A., Naggar, E. F., Rich, C. B., et al. (2006). Neutrophil elastase-initiated EGFR/ MEK/ ERK signaling counteracts stabilizing effect of autocrine TGF-beta on tropoelastin mRNA in lung fibroblasts. American Journal of Physiology. Lung Cellular and Molecular Physiology, 291, L232–L243.

    Article  PubMed  CAS  Google Scholar 

  60. Werner, S., & Grose, R. (2003). Regulation of wound healing by growth factors and cytokines. Physiological Reviews, 83, 835–870.

    PubMed  CAS  Google Scholar 

  61. Ware, L. B., & Matthay, M. A. (2002). Keratinocyte and hepatocyte growth factors in the lung: Roles in lung development, inflammation, and repair. American Journal of Physiology. Lung Cellular and Molecular Physiology, 282, L924–L940.

    PubMed  CAS  Google Scholar 

  62. Ingram, J. L., & Bonner, J. C. (2006). EGF and PDGF receptor tyrosine kinases as therapeutic targets for chronic lung diseases. Current Molecular Medicine, 6(4), 409–421.

    Article  PubMed  CAS  Google Scholar 

  63. Yildirim, A. O., Veith, M., Rausch, T., Müller, B., Kilb, P., Van Winkle, L. S., et al. (2008). Keratinocyte growth factor protects against Clara cell injury induced by naphthalene. European Respiratory Journal, 32(3), 694–704.

    Article  PubMed  CAS  Google Scholar 

  64. de Boer, W. I., Alagappan, V. K., & Sharma, H. S. (2007). Molecular mechanisms in chronic obstructive pulmonary disease: Potential targets for therapy. Cell Biochemistry and Biophysics, 47(1), 131–148.

    PubMed  Google Scholar 

  65. de Boer, W. I., van Schadewijk, A., Sont, J. K., Sharma, H. S., Stolk, J., Hiemstra, P. S., et al. (1998). Transforming growth factor beta1 and recruitment of macrophages and mast cells in airways in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 158(6), 1951–1957.

    Article  PubMed  Google Scholar 

  66. Barnes, P. J. (2009). The cytokine network in chronic obstructive pulmonary disease. American Journal of Respiratory Cell and Molecular Biology, 41, 631–638.

    Article  PubMed  CAS  Google Scholar 

  67. Elsasser, T. H. (2003). Insulin-like growth factor-I: A traffic control device on the road to tissue recovery. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 285, R22–R23.

    Google Scholar 

  68. Kranenburg, A. R., Willems-Widyastuti, A., Mooi, W. J., Saxena, P. R., Sterk, P. J., de Boer, W. I., et al. (2005). Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1, FGF-2, and FGFR-1. Journal of Pathology, 206(1), 28–38.

    Article  PubMed  CAS  Google Scholar 

  69. Carmeliet, P., & Jain, R. K. (2011). Molecular mechanisms and clinical applications of angiogenesis. Nature, 473(7347), 298–307.

    Article  PubMed  CAS  Google Scholar 

  70. Cross, M. J., & Claesson-Welsh, L. (2001). FGF and VEGF function in angiogenesis: Signalling pathways, biological responses and therapeutic inhibition. Trends in Pharmacological Sciences, 22(4), 201–207.

    Article  PubMed  CAS  Google Scholar 

  71. Tuder, R. M., Flook, B. E., & Voelkel, N. F. (1995). Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. Journal of Clinical Investigation, 95(4), 1798–1807.

    Article  PubMed  CAS  Google Scholar 

  72. Alagappan, V. K., Willems-Widyastuti, A., Seynhaeve, A. L., Garrelds, I. M., ten Hagen, T. L., Saxena, P. R., et al. (2007). Vasoactive peptides upregulate mRNA expression and secretion of vascular endothelial growth factor in human airway smooth muscle cells. Cell Biochemistry and Biophysics, 47(1), 109–118.

    PubMed  CAS  Google Scholar 

  73. Shehata, S. M., Mooi, W. J., Okazaki, T., El-Banna, I., Sharma, H. S., & Tibboel, D. (1999). Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension. Thorax, 54(5), 427–431.

    Article  PubMed  CAS  Google Scholar 

  74. Hoshino, M., Nakamura, Y., & Hamid, Q. A. (2001). Gene expression of vascular endothelial growth factor and its receptors and angiogenesis in bronchial asthma. Journal of Allergy and Clinical Immunology, 107(6), 1034–1038.

    Article  PubMed  CAS  Google Scholar 

  75. Hamrah, P., Chen, L., Zhang, Q., & Dana, M. R. (2003). Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on corneal dendritic cells. American Journal of Pathology, 163(1), 57–68.

    Article  PubMed  CAS  Google Scholar 

  76. Kanazawa, H., Asai, K., Hirata, K., & Yoshikawa, J. (2003). Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. American Journal of Medicine, 114, 354–358.

    Article  PubMed  CAS  Google Scholar 

  77. Le Cras, T. D., Spitzmiller, R. E., Albertine, K. H., Greenberg, J. M., Whitsett, J. A., & Akeson, A. L. (2004). VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice. American Journal of Physiology. Lung Cellular and Molecular Physiology, 287, L134–L142.

    Article  PubMed  Google Scholar 

  78. Tsao, P. N., Su, Y. N., Li, H., Huang, P. H., Chien, C. T., Lai, Y. L., et al. (2004). Overexpression of placenta growth factor contributes to the pathogenesis of pulmonary emphysema. American Journal of Respiratory and Critical Care Medicine, 169(4), 505–511.

    Article  PubMed  Google Scholar 

  79. Medford, A. R. L., & Millar, A. B. (2006). Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): Paradox or paradigm? Thorax, 61(7), 621–626.

    Article  PubMed  CAS  Google Scholar 

  80. Coumoul, X., & Deng, C. X. (2003). Roles of FGF receptors in mammalian development and congenital diseases. Birth Defects Research Part C: Embryo Today, 69, 286–304.

    Article  CAS  Google Scholar 

  81. Kim, I., Moon, S., Yu, K., Kim, U., & Koh, G. Y. (2001). A novel fibroblast growth factor receptor-5 preferentially expressed in the pancreas. Biochimica et Biophysica Acta, 1518, 152–156.

    Article  PubMed  CAS  Google Scholar 

  82. Szebenyi, G., & Fallon, J. F. (1999). Fibroblast growth factors as multifunctional signaling factors. International Review of Cytology, 185, 45–106.

    Article  PubMed  CAS  Google Scholar 

  83. Yum, H. Y., Cho, J. Y., Miller, M., & Broide, D. H. (2011). Allergen-induced coexpression of bFGF and TGF-β1 by macrophages in a mouse model of airway remodeling: bFGF induces macrophage TGF-β1 expression in vitro. International Archives of Allergy and Immunology, 155(1), 12–22.

    Article  PubMed  CAS  Google Scholar 

  84. Shute, J. K., Solic, N., Shimizu, J., McConnell, W., Redington, A. E., & Howarth, P. H. (2004). Epithelial expression and release of FGF-2 from heparan sulphate binding sites in bronchial tissue in asthma. Thorax, 59, 557–562.

    Article  PubMed  CAS  Google Scholar 

  85. Becerril, C., Pardo, A., Montano, M., Ramos, C., Ramirez, R., & Selman, M. (1999). Acidic fibroblast growth factor induces an antifibrogenic phenotype in human lung fibroblasts. American Journal of Respiratory Cell and Molecular Biology, 20, 1020–1027.

    Article  PubMed  CAS  Google Scholar 

  86. Hughes, S. E., & Hall, P. A. (1993). Immunolocalization of fibroblast growth factor receptor 1 and its ligands in human tissues. Laboratory Investigation, 69(2), 173–182.

    PubMed  CAS  Google Scholar 

  87. Singh, T. M., Abe, K. Y., Sasaki, T., Zhuang, Y. J., Masuda, H., & Zarins, C. K. (1998). Basic fibroblast growth factor expression precedes flow-induced arterial enlargement. Journal of Surgical Research, 77(2), 165–173.

    Article  PubMed  CAS  Google Scholar 

  88. Bryant, S. R., Bjercke, R. J., Erichsen, D. A., Rege, A., & Lindner, V. (1999). Vascular remodeling in response to altered blood flow is mediated by fibroblast growth factor-2. Circulation Research, 84(3), 323–328.

    Article  PubMed  CAS  Google Scholar 

  89. Creutzberg, E. C., & Casaburi, R. (2003). Endocrinological disturbances in chronic obstructive pulmonary disease. European Respiratory Journal Supplement, 46, 76s–80s.

    Article  CAS  Google Scholar 

  90. Yu, H., & Rohan, T. (2000). Role of the insulin-like growth factor family in cancer development and progression. Journal of the National Cancer Institute, 92, 1472–1489.

    Article  PubMed  CAS  Google Scholar 

  91. Alagappan, V. K. T., Kranenburg, A. R., Widyastuti, A., Saxena, P. R., & Sharma, H. S. (2003). Insulin-like growth factors stimulate proliferation and growth of cultured human airway epithelial but not smooth muscle cells. American Journal of Respiratory and Critical Care Medicine, 167, A32.

    Article  Google Scholar 

  92. Halwani, R., Al-Muhsen, S., Al-Jahdali, H., & Hamid, Q. (2011). Role of transforming growth factor-β in airway remodeling in asthma. American Journal of Respiratory Cell and Molecular Biology, 44(2), 127–133.

    Article  PubMed  CAS  Google Scholar 

  93. Ling Chen, L., Ge, Q., Black, J. L., Deng, L., Burgess, J. K., & Oliver, B. G. G. (2013). Differential regulation of extracellular matrix and soluble fibulin-1 levels by TGF-β1 in airway smooth muscle cells. PLoS ONE, 8(6), e65544.

    Article  PubMed  CAS  Google Scholar 

  94. Reddel, C. J., Cultrone, D., Rnjak-Kovacina, J., Weiss, A. S., & Burgess, J. K. (2013). Tropoelastin modulates TGF-β1-induced expression of VEGF and CTGF in airway smooth muscle cells. Matrix Biology,. doi:10.1016/j.matbio.2013.04.003.

    PubMed  Google Scholar 

  95. Willems-Widyastuti, A., Alagappan, V. K., Arulmani, U., Vanaudenaerde, B. M., de Boer, W. I., Mooi, W. J., et al. (2011). Transforming growth factor-beta 1 induces angiogenesis in vitro via VEGF production in human airway smooth muscle cells. Indian Journal of Biochemistry and Biophysics, 48(4), 262–269.

    PubMed  CAS  Google Scholar 

  96. Howarth, P. H., Knox, A. J., Amrani, Y., Tliba, O., Panettieri, J., Reynold, A., et al. (2004). Synthetic responses in airway smooth muscle. Journal of Allergy and Clinical Immunology, 114, S32–S50.

    Article  PubMed  CAS  Google Scholar 

  97. Lazaar, A. L., & Panettieri, R. A, Jr. (2005). Airway smooth muscle: A modulator of airway remodeling in asthma. Journal of Allergy and Clinical Immunology, 116, 488–495. quiz 96.

    Article  PubMed  Google Scholar 

  98. Koziol-White, C. J., & Panettieri, R. A, Jr. (2011). Airway smooth muscle and immune-modulation in acute exacerbations of airway disease. Immunological Reviews, 42(1), 178–185.

    Article  Google Scholar 

  99. Amrani, Y., & Panettieri, R. A. (2003). Airway smooth muscle: Contraction and beyond. International Journal of Biochemistry and Cell Biology, 35, 272–276.

    Article  PubMed  CAS  Google Scholar 

  100. Dekkers, B. G., Maarsingh, H., Meurs, H., & Gosens, R. (2009). Airway structural components drive airway smooth muscle remodeling in asthma. Proceedings of the American Thoracic Society, 6(8), 683–692.

    Article  PubMed  CAS  Google Scholar 

  101. Black, J. L., Roth, M., Lee, J., Carlin, S., & Johnson, P. R. (2001). Mechanisms of airway remodeling. Airway smooth muscle. American Journal of Respiratory and Critical Care Medicine, 164, S63–S66.

    Article  PubMed  CAS  Google Scholar 

  102. Mitzner, W. (2004). Airway smooth muscle: The appendix of the lung. American Journal of Respiratory and Critical Care Medicine, 169, 787–790.

    Article  PubMed  Google Scholar 

  103. McKay, S., de Jongste, J. C., Saxena, P. R., & Sharma, H. S. (1998). Angiotensin II induces hypertrophy of human airway smooth muscle cells: Expression of transcription factors and transforming growth factor-beta1. American Journal of Respiratory Cell and Molecular Biology, 18, 823–833.

    Article  PubMed  CAS  Google Scholar 

  104. Alagappan, V. K., McKay, S., Widyastuti, A., Garrelds, I. M., Bogers, A. J., Hoogsteden, H. C., et al. (2005). Proinflammatory cytokines upregulate mRNA expression and secretion of vascular endothelial growth factor in cultured human airway smooth muscle cells. Cell Biochemistry and Biophysics, 43, 119–130.

    Article  PubMed  CAS  Google Scholar 

  105. Knox, A. J., Corbett, L., Stocks, J., Holland, E., Zhu, Y. M., & Pang, L. (2001). Human airway smooth muscle cells secrete vascular endothelial growth factor: Up-regulation by bradykinin via a protein kinase C and prostanoid-dependent mechanism. Faseb Journal, 15, 2480–2488.

    Article  PubMed  CAS  Google Scholar 

  106. Kumar, A., Knox, A. J., & Boriek, A. M. (2003). CCAAT/enhancer-binding protein and activator protein-1 transcription factors regulate the expression of interleukin-8 through the mitogen-activated protein kinase pathways in response to mechanical stretch of human airway smooth muscle cells. Journal of Biological Chemistry, 278, 18868–18876.

    Article  PubMed  CAS  Google Scholar 

  107. Santos, S., Peinado, V. I., Ramirez, J., Morales-Blanhir, J., Bastos, R., & Roca, J. (2003). Enhanced expression of vascular endothelial growth factor in pulmonary arteries of smokers and patients with moderate chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 167, 1250–1256.

    Article  PubMed  Google Scholar 

  108. Hirst, S. J. (1996). Airway smooth muscle cell culture: Application to studies of airway wall remodelling and phenotype plasticity in asthma. European Respiratory Journal, 9, 808–820.

    Article  PubMed  CAS  Google Scholar 

  109. Sharma, H. S., Alagappan, V. K. T., Garrelds, I. M., Hoogsteden, H. C., & Bogers, A. J. J. C. (2004). Proliferating airway smooth muscle cell secrete factors for pulmonary endothelial cell growth: Role of vascular endothelial growth factor. American Journal of Respiratory and Critical Care Medicine, 169, A16.

    Google Scholar 

  110. Jain, R. K., Duda, D. G., Clark, J. W., & Loeffler, J. S. (2006). Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nature Clinical Practice Oncology, 3, 24–40.

    Article  PubMed  CAS  Google Scholar 

  111. Ferrara, N., Gerber, H. P., & LeCouter, J. (2003). The biology of VEGF and its receptors. Nature Medicine, 9(6), 669–676.

    Article  PubMed  CAS  Google Scholar 

  112. Ruggeri, B., Singh, J., & Gingrich, D. (2003). CEP-7055: A novel, orally active pan inhibitor of vascular endothelial growth factor receptor tyrosine kinases with potent antiangiogenic activity and antitumor efficacy in preclinical models. Cancer Research, 63(18), 5978–5991.

    PubMed  CAS  Google Scholar 

  113. Konner, J., & Dupont, J. (2004). Use of soluble recombinant decoy receptor vascular endothelial growth factor trap (VEGF Trap) to inhibit vascular endothelial growth factor activity. Clinical Colorectal Cancer, 4(Suppl 2), S81–S85.

    Article  PubMed  CAS  Google Scholar 

  114. Cursiefen, C., Chen, L., Borges, L. P., et al. (2004). VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. Journal of Clinical Investigation, 113(7), 1040–1050.

    PubMed  CAS  Google Scholar 

  115. Underiner, T. L., Ruggeri, B., & Gingrich, D. E. (2004). Development of vascular endothelial growth factor receptor (VEGFR) kinase inhibitors as anti-angiogenic agents in cancer therapy. Current Medicinal Chemistry, 11(6), 731–745.

    Article  PubMed  CAS  Google Scholar 

  116. Le Cras, T. D., Spitzmiller, R. E., Albertine, K. H., Greenberg, J. M., Whitsett, J. A., & Akeson, A. L. (2004). VEGF causes pulmonary hemorrhage, hemosiderosis, and air space enlargement in neonatal mice. American Journal of Physiology. Lung Cellular and Molecular Physiology, 287(1), L134–L142.

    Article  PubMed  Google Scholar 

  117. Lee, C. G., Link, H., Baluk, P., et al. (2004). Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nature Medicine, 10(10), 1095–1103.

    Article  PubMed  CAS  Google Scholar 

  118. Ton, N. C., & Jayson, G. C. (2004). Resistance to anti-VEGF agents. Current Pharmaceutical Design, 10(1), 51–64.

    Article  PubMed  CAS  Google Scholar 

  119. Barnes, P. J. (2013). Development of new drugs for COPD. Current Medicinal Chemistry, 20(12), 1531–1540.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pulmonary Division, Novartis, Horsham, UK

    Vijay K. T. Alagappan

  2. Department of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands

    Willem I. de Boer

  3. Institute of Cardiac Sciences, Sheikh Khalifa Medical City-Cleveland Clinic, Abu Dhabi, UAE

    Virendra K. Misra

  4. Department of Pathology, VU University Medical Center (VUmc), De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Vijay K. T. Alagappan, Wolter J. Mooi & Hari S. Sharma

Authors
  1. Vijay K. T. Alagappan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Willem I. de Boer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Virendra K. Misra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wolter J. Mooi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hari S. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hari S. Sharma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alagappan, V.K.T., de Boer, W.I., Misra, V.K. et al. Angiogenesis and Vascular Remodeling in Chronic Airway Diseases. Cell Biochem Biophys 67, 219–234 (2013). https://doi.org/10.1007/s12013-013-9713-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-013-9713-6

Keywords

Search

Navigation