Current Allergy and Asthma Reports

, Volume 3, Issue 2, pp 153–158 | Cite as

Airway vascular remodeling in asthma

  • John W. Wilson
  • Tom Kotsimbos


Several characteristic changes occur in the bronchial wall in asthma, including specific changes to the vasculature. These result in an increase in vessel numbers per unit area, as well as increased vessel activity suggested by vasodilatation, vessel leakage, and cellular margination with transmigration to target tissues. This combined action in asthma leads to airway-wall thickening and reduced airflow. Each component of the vascular response has been shown to be controlled by a range of inflammatory mediators and growth factors. These factors are themselves regulated by a complex process initially involving gene expression, transcription, and translation at the molecular level, then subsequent protein release, binding to matrix elements, endothelial cell activation, and a proliferative endothelial response. Many commonly used airway medications are capable of modulating the vascular response to inflammatory stimuli. New therapies might improve airflow through better regulation of vessel growth, dilatation, and leakage in the airway wall.


Asthma Vascular Endothelial Growth Factor Airflow Obstruction Airway Wall Vascular Endothelial Cell Growth Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Wilson J: The bronchial microcirculation in asthma. Clin Exp Allergy 2000, 30:51–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Corfield DR, Hanafi Z, Webber SE, Widdicombe JG: Changes in tracheal mucosal thickness and blood flow in sheep. J Appl Physiol 1991, 71:1282–1288.PubMedGoogle Scholar
  3. 3.
    McDonald DM: The ultrastructure and permeability of tracheobronchial blood vessels in health and disease. Eur Respir J 1990, 12:572S-585S.Google Scholar
  4. 4.
    Widdicombe J: Why are the airways so vascular? Thorax 1993, 48:290–295. A useful description of the anatomy of airway circulation.PubMedCrossRefGoogle Scholar
  5. 5.
    Jakeman LB, Armanini M, Phillips HS, Ferrara N: Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology 1993, 133:848–859.PubMedCrossRefGoogle Scholar
  6. 6.
    deVries C, Escobedo JA, Ueno H, et al.: The fms-like tyrosine kinase: a receptor for vascular endothelial growth factor. Science 1992, 255:989–991.CrossRefGoogle Scholar
  7. 7.
    Terman BI, Dougher-Vermazen M, Carrion ME, et al.: Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Comm 1992, 187:1579–1586.PubMedCrossRefGoogle Scholar
  8. 8.
    Morishita K, Johnson DE, Williams LT: A novel promoter for vascular endothelial growth factor receptor (flt-1) that confers endothelial-specific gene expression. J Biol Chem 1995, 270:27948–27953.PubMedCrossRefGoogle Scholar
  9. 9.
    Patterson C, Perrella MA, Hsieh CM, et al.: Cloning and functional analysis of the promoter for KDR/flk-1, a receptor for vascular endothelial growth factor. J Biol Chem 1995, 270:23111–23118.PubMedCrossRefGoogle Scholar
  10. 10.
    Wegner CD, Wolyniec WW, La Plante, et al.: Intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of asthma. Science 1990, 247:456–459. This description of blockade of ICAM-1 is an important demonstration of the importance of the role of vessels and adhesion glycoproteins in asthma.PubMedCrossRefGoogle Scholar
  11. 11.
    Maisonpierre PC, Suri C, Jones PF, et al.: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997, 277:55–60.PubMedCrossRefGoogle Scholar
  12. 12.
    O’Reilly M, Silver GM, Gamelli RL, et al.: Dose dependency of granulocyte-macrophage colony stimulating factor for improving survival following burn wound infection. J Trauma 1994, 36:486–490.PubMedCrossRefGoogle Scholar
  13. 13.
    Auerbach W, Auerbach R: Angiogenesis inhibition: a review. Pharmacol Ther 1994, 63:265–311.PubMedCrossRefGoogle Scholar
  14. 14.
    Voest EE, Kenyon BM, O’Reilly MS, et al.: Inhibition of angiogenesis in vivo by interleukin 12. J Natl Cancer Inst 1995, 87:581–586.PubMedCrossRefGoogle Scholar
  15. 15.
    Strieter RM: Chemokines: not just leukocyte chemoattractants in the promotion of cancer. 2001, 2:285-286. A good summary of potential roles of growth factors in angiogenesis.Google Scholar
  16. 16.
    Carroll N, Elliott J, Morton A, James A: The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 1993, 147:405–410.PubMedGoogle Scholar
  17. 17.
    Kuwano K, Bosken CH, Pare PD, et al.: Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993, 148:1220–1225.PubMedGoogle Scholar
  18. 18.
    Djukanovic R, Wilson JW, Lai CK, et al.: The safety aspects of fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy in asthma. Am Rev Respir Dis 1991, 143(4 Pt 1):772–777.PubMedGoogle Scholar
  19. 19.
    Carroll NG, Cooke C, James AL: Bronchial blood vessel dimensions in asthma. Am J Respir Crit Care Med 1997, 155:689–695.PubMedGoogle Scholar
  20. 20.
    Li X, Wilson JW: Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med 1997, 156:229–233. The first description of the use of collagen IV as a marker for vessels in airway biopsies in asthma.PubMedGoogle Scholar
  21. 21.
    Wilson JW, Bamford TL: Assessing the evidence for remodelling of the airway in asthma. Pulm Pharmacol 2001, 14:229–247.CrossRefGoogle Scholar
  22. 22.
    Bradding P, Holgate ST: Immunopathology and human mast cell cytokines. Crit Rev Oncol Hematol 1999, 31:119–133.PubMedGoogle Scholar
  23. 23.
    Holgate ST, Djukanovic P, Wilson J, et al.: Allergic inflammation and its pharmacological modulation in asthma. Int Arch Allergy Appl Immunol 1991, 94:210–217.PubMedGoogle Scholar
  24. 24.
    Lovett D, Kozan B, Hadam M, et al.: Macrophage cytotoxicity: interleukin 1 as a mediator of tumor cytostasis. J Immunol 1986, 136:340–347.PubMedGoogle Scholar
  25. 25.
    Bradding P, Roberts JA, Britten KM, et al.: Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 1994, 10:471–480.PubMedGoogle Scholar
  26. 26.
    D’Amore PA: Mechanisms of endothelial growth control. Am J Respir Cell Mol Biol 1992, 6:1–8.PubMedGoogle Scholar
  27. 27.
    Ferrara N, Henzel WJ: Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Comm 1989, 161:851–858.PubMedCrossRefGoogle Scholar
  28. 28.
    Dunnill MS: The pathology of asthma, with special reference to the bronchial mucosa. J Clin Pathol 1960, 13:27–33.PubMedGoogle Scholar
  29. 29.
    Wilson JW, Wilson SJ: The bronchial microcirculation. Clin Exp Allergy Revs 2001, 1:120–122.CrossRefGoogle Scholar
  30. 30.
    McDonald DM: Neurogenic inflammation in the rat trachea. I. Changes in venules, leucocytes and epithelial cells. J Neurocytol 1988, 17:583–603.PubMedCrossRefGoogle Scholar
  31. 31.
    McDonald DM, Mitchell RA, Gabella G, Haskell A: Neurogenic inflammation in the rat trachea. II. Identity and distribution of nerves mediating the increase in vascular permeability. J Neurocytol 1988, 17:605–628.PubMedCrossRefGoogle Scholar
  32. 32.
    Wiggs BR, Bosken C, Pare PD, et al.: A model of airway narrowing in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992, 145:1251–1258.PubMedGoogle Scholar
  33. 33.
    Mitzner W, Wagner E, Brown RH: Is asthma a vascular disorder? Chest 1995, 107(3 Suppl):97S-102S. A key reference that summarizes the importance of modeling studies identifying the role of bronchial vessels in airflow obstruction.PubMedGoogle Scholar
  34. 34.
    Wilson JW, Li X, Pain MC: The lack of distensibility of asthmatic airways. Am Rev Respir Dis 1993, 148:806–809.PubMedGoogle Scholar
  35. 35.
    Wilson JW, Li X: The measurement of reticular basement membrane and submucosal collagen in the asthmatic airway [see comments]. Clin Exper Allergy 1997, 27:363–371.CrossRefGoogle Scholar
  36. 36.
    Ebina M, Takahashi T, Chiba T, Motomiya M: Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma: a 3-D morphometric study. Am Rev Respir Dis 1993, 148:720–726.PubMedGoogle Scholar
  37. 37.
    Smith JC, Mitzner W: Elastic characteristics of the lung perivascular interstitial space. J Appl Physiol 1983, 54:1717–1725.PubMedCrossRefGoogle Scholar
  38. 38.
    Rushmer FJ: Cardiovascular Dynamics, 2nd edn. Philadelphia: WB Saunders; 1961:470–471.Google Scholar
  39. 39.
    Gleason DC, Steiner RE: The lateral roentgenogram in pulmonary edema. Am J Roentgenol Rad Ther Nucl Med 1966, 98:279–290.Google Scholar
  40. 40.
    Cabanes LR, Weber SN, Matran R, et al.: Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function. N Engl J Med 1989, 320:1317–1322.PubMedCrossRefGoogle Scholar
  41. 41.
    Wagner EM, Mitzner WA: Effect of left atrial pressure on bronchial vascular hemodynamics. J Appl Physiol 1990, 69:837–842.PubMedGoogle Scholar
  42. 42.
    Brown RH, et al.: In vivo measurements of airway reactivity using high-resolution computed tomography. Am Rev Respir Dis 1991, 144:208–212.PubMedGoogle Scholar
  43. 43.
    Brown RH, Herold CJ, Hirshman CA, et al.: Individual airway constrictor response heterogeneity to histamine assessed by high-resolution computed tomography. J Appl Physiol 1993, 74:2615–2620.PubMedGoogle Scholar
  44. 44.
    Lockhart A, Dinh-Xuan AT, Regnard J, et al.: Effect of airway blood flow on airflow. Am Rev Respir Dis 1992, 146(5 Pt 2):S19–23.PubMedGoogle Scholar
  45. 45.
    Laitinen LA, Laitinen MA, Widdicombe JG: Dose-related effects of pharmacological mediators on tracheal vascular resistance in dogs. Br J Pharmacol 1987, 92:703–709.PubMedGoogle Scholar
  46. 46.
    Orsida BE, Ward C, Li X, et al.: Effect of a long-acting beta2-agonist over three months on airway wall vascular remodeling in asthma. Am J Respir Critl Care Med 2001, 164:117–121.Google Scholar
  47. 47.
    Orsida BE, Li X, Hickey B, et al.: Vascularity in asthmatic airways: relation to inhaled steroid dose. Thorax 1999, 54:289–295.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2003

Authors and Affiliations

  • John W. Wilson
    • 1
  • Tom Kotsimbos
    • 1
  1. 1.Department of Respiratory Medicine and Monash Medical SchoolThe Alfred HospitalPrahranAustralia

Personalised recommendations