Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Respiratory Research
Published in: Respiratory Research 1/2010

Open Access 01-12-2010 | Review

The role of the bronchial microvasculature in the airway remodelling in asthma and COPD

Authors: Andrea Zanini, Alfredo Chetta, Andrea S Imperatori, Antonio Spanevello, Dario Olivieri

Published in: Respiratory Research | Issue 1/2010

Login to get access

Abstract

In recent years, there has been increased interest in the vascular component of airway remodelling in chronic bronchial inflammation, such as asthma and COPD, and in its role in the progression of disease. In particular, the bronchial mucosa in asthmatics is more vascularised, showing a higher number and dimension of vessels and vascular area. Recently, insight has been obtained regarding the pivotal role of vascular endothelial growth factor (VEGF) in promoting vascular remodelling and angiogenesis. Many studies, conducted on biopsies, induced sputum or BAL, have shown the involvement of VEGF and its receptors in the vascular remodelling processes. Presumably, the vascular component of airway remodelling is a complex multi-step phenomenon involving several mediators. Among the common asthma and COPD medications, only inhaled corticosteroids have demonstrated a real ability to reverse all aspects of vascular remodelling. The aim of this review was to analyze the morphological aspects of the vascular component of airway remodelling and the possible mechanisms involved in asthma and COPD. We also focused on the functional and therapeutic implications of the bronchial microvascular changes in asthma and COPD.
Literature
1.
2.
3.
Charan NB, Baile EM, Pare PD: Bronchial vascular congestion and angiogenesis. Eur Respir J 1997, 10:1173–1180.CrossRefPubMed
4.
John GW: Microvascular anatomy of the airways. In Asthma and rhinitis. 2nd edition. Edited by: Willium WB, Stephen TH. Malden, MA: Blackwell Science; 2000:721–731.
5.
Deffebach ME: Lung mechanical effects on the bronchial circulation. Eur Respir J Suppl 1990, 12:586s-590s.PubMed
6.
Lung MAKY, Wang JCC, Cheng KK: Bronchial circulation: an auto-perfusion method for assessing its vasomotor acitivity and the study of alpha- and beta-adrenoceptors in the bronchial artery. Life Sci 1976, 19:577–580.CrossRefPubMed
7.
Lieckens S: Angiogenesis: regulators and clinical applications. Biochem Pharmacol 2001, 61:253–270.CrossRef
8.
Deffebach ME, Charan NB, Lakshminarayan S, Butler J: The bronchial circulation. Small, but a vital attribute of the lung. Am Rev Respir Dis 1987, 135:463–480.PubMed
9.
Walters EH, Reid D, Soltani A, Ward C: Angiogenesis: a potentially critical part of remodelling in chronic airway diseases? Pharmacol Ther 2008, 118:128–137.CrossRefPubMed
10.
McDonald DM: Angiogenesis and remodeling of airway vasculature in chronic inflammation. Am J Respir Crit Care Med 2001, 164:S39-S45.CrossRefPubMed
11.
Carroll NG, Cooke C, James AL: Bronchial blood vessels dimensions in asthma. Am J Respir Crit Care Med 1997, 155:689–695.CrossRefPubMed
12.
Li X, Wilson JW: Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med 1997, 156:229–233.CrossRefPubMed
13.
Salvato G: Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects. Thorax 2001, 56:902–906.CrossRefPubMedPubMedCentral
14.
Wilson JW, Hii S: The importance of the airway microvasculature in asthma. Curr Opin Allergy Clin Immunol 2006, 6:51–55.CrossRefPubMed
15.
Chetta A, Zanini A, Torre O, Olivieri D: Vascular remodelling and angiogenesis in asthma: morphological aspects and pharmacological modulation. Inflamm Allergy Drug Targets 2007, 1:41–45.CrossRef
16.
17.
Hashimoto M, Tanaka H, Abe S: Quantitative analysis of bronchial wall vascularity in the medium and small airways of patients with asthma and COPD. Chest 2005, 127:965–972.CrossRefPubMed
18.
Calabrese C, Bocchino V, Vatrella A, Marzo C, Guarino C, Mascitti S, Tranfa CME, Cazzola M, Micheli P, Caputi M, Marsico SA: Evidence of angiogenesis in bronchial biopsies of smokers with and without airway obstruction. Resp Med 2006, 100:1415–1422.CrossRef
19.
20.
Dunnill MS, Massarella GR, Anderson JA: A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis and in emphysema. Thorax 1969, 24:176–179.CrossRefPubMedPubMedCentral
21.
Kuwano K, Bosken CH, Paré PD, Bai TR, Wiggs BR, Hogg JC: Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993, 148:1220–1225.CrossRefPubMed
22.
Kumar SD, Emery MJ, Atkins ND, Danta I, Wanner A: Airway mucosal blood flow in bronchial asthma. Am J Respir Crit Care Med 1998, 158:153–156.CrossRefPubMed
23.
Bailey SR, Boustany S, Burgess JK, Hirst SJ, Sharma HS, Simcock DE, Suravaram PR, Weckmann M: Airway vascular reactivity and vascularisation in human chronic airway disease. Pulm Pharmacol Ther 2009, 22:417–425.CrossRefPubMed
24.
Charan NB, Johnson SR, Lakshminarayan S, Thompson WH, Carvalho P: Nitric oxide and beta-adrenergic agonist-induced bronchial arterial vasodilation. J Appl Physiol 1997, 82:686–692.PubMed
25.
26.
Chung KF, Rogers DF, Barnes PJ, Evans TW: The role of increased airway microvascular permeability and plasma exudation in asthma. Eur Respir J 1990, 3:329–337.PubMed
27.
McDonald DM: The ultrastructure and permeability of tracheobronchial blood vessels in health and disease. Eur Respir J 1990,12(Suppl):572–585.
28.
Asai K, Kanazawa H, Kamoi H, Shiraishi S, Hirata K, Yoshikawa J: Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients. Clin Exp Allergy 2003, 33:595–599.CrossRefPubMed
29.
Kanazawa H, Nomura S, Yoshikawa J: Role of microvascular permeability on physiologic differences in asthma and eosinophilic bronchitis. Am J Respir Crit Care Med 2004, 169:1125–1130.CrossRefPubMed
30.
Kanazawa H, Hirata H, Yoshikawa J: Involvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients. Thorax 2002, 57:885–888.CrossRefPubMedPubMedCentral
31.
Kanazawa H, Nomura S, Asai K: Roles of angiopoietin-1 and angiopoietin-2 on airway microvascular permeability in asthmatic patients. Chest 2007, 131:1035–1041.CrossRefPubMed
32.
Meerschaert J, Becky Kelly EA, Mosher DF, Busse WW, Jarjour NN: Segmental antigen challenge increases fibronectin in bronchoalveolar lavage fluid. Am J Respir Crit Care Med 1999, 159:619–625.CrossRefPubMed
33.
Svensson C, Grönneberg R, Andersson M, Alkner U, Andersson O, Billing B, Gilljam H, Greiff L, Persson CGA: Allergen challenge-induced entry of alpha 2-macroglobulin and tryptase into human nasal and bronchial airways. J Allergy Clin Immunol 1995, 96:239–246.CrossRefPubMed
34.
Goldie RG, Pedersen KE: Mechanisms of increased airway microvascular permeability: role in airway inflammation and obstruction. Clin Exp Pharmacol Physiol 1995, 22:387–396.CrossRefPubMed
35.
James AL, Pare PD, Hogg JC: The mechanics of airway narrowing in asthma. Am Rev Respir Dis 1989, 139:242–246.CrossRefPubMed
36.
Otani K, Kanazawa H, Fujiwara H, Hirata K, Fujimoto S, Yoshikawa J: Determinants of the severity of exercise-induced bronchoconstriction in patients with asthma. J Asthma 2004, 41:271–278.CrossRefPubMed
37.
Roberts WG, Palade GE: Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 1995, 108:2369–2379.PubMed
38.
Greiff L, Wollmer P, Andersson M, Svensson C, Persson CGA: Effects of formoterol on histamine induced plasma exudation in induced sputum from normal subjects. Thorax 1998, 53:1010–1013.CrossRefPubMedPubMedCentral
39.
Berman AR, Liu MC, Wagner EM, Proud D: Dissociation of bradykinin-induced plasma exudation and reactivity in the peripheral airways. Am J Respir Crit Care Med 1996, 154:418–423.CrossRefPubMed
40.
Cudkowicz L: Leonardo da Vinci and the bronchial circulation. Br J Dis Chest 1953, 47:649–670.
41.
Folkman J: Clinical applications of research on angiogenesis. New Engl J Med 1995, 333:1951–1957.
42.
Chetta A, Zanini A, Foresi A, Del Donno M, Castagnaro A, D'Ippolito R, Baraldo S, Testi R, Saetta M, Olivieri D: Vascular component of airway remodelling in asthma is reduced by high dose of fluticasone. Am J Respir Crit Care Med 2003, 167:751–757.CrossRefPubMed
43.
Tanaka H, Yamada G, Saikai T, Hashimoto M, Tanaka S, Suzuki K, Fujii M, Takahashi H, Abe S: Increased airway vascularity in newly diagnosed asthma using a high-magnification bronchovideoscope. Am J Respir Crit Care Med 2003, 168:1495–1499.CrossRefPubMed
44.
Yamada G, Takahashi H, Shijubo N, Itoh T, Abe S: Subepithelial microvasculature in large airways observed by high-magnification bronchovideoscope. Chest 2005, 128:876–880.CrossRefPubMed
45.
Orsida BE, Li X, Hickey B, Thien F, Wilson JW, Walters EH: Vascularity in asthmatic airways: relation to inhaled steroid dose. Thorax 1999, 54:289–295.CrossRefPubMedPubMedCentral
46.
Hoshino M, Takahashi M, Takai Y, Sim J, Aoike N: Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma. Clin Exp Allergy 2001, 31:722–730.CrossRefPubMed
47.
Feltis NB, Wignarajah D, Zheng L, Ward C, Reid D, Harding R, Walters EH: Increased vascular endothelial growth factor and receptors. Am J Respir Crit Care Med 2006, 173:1201–1207.CrossRefPubMed
48.
Barbato A, Turato G, Baraldo S, Bazzan E, Calabrese F, Panizzolo C, Zanin ME, Zuin R, Maestrelli P, Fabbri LM, Saetta M: Epithelial damage and angiogenesis in the airways of children with asthma. Am J Respir Crit Care Med 2006, 174:975–981.CrossRefPubMed
49.
Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Beliën JAM, de Waal RMW, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY: Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 2002, 38:1564–1579.CrossRefPubMed
50.
Vrugt B, Wilson S, Bron A, Holgate ST, Djukanovic R, Aalbers R: Bronchial angiogenesis in severe glucocorticoid-dependent asthma. Eur Respir J 2000, 15:1014–1021.CrossRefPubMed
51.
Walters EH, Soltani A, Reid DW, Ward C: Vascular remodelling in asthma. Curr Opinion Allergy Clin Immunol 2008, 8:39–43.CrossRef
52.
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, 107:295–301.CrossRefPubMed
53.
Hoshino M, Nakamura Y, Hamid Q: Gene expression of vascular endothelial growth factor and its receptors and angiogenesis in bronchial asthma. J Allergy Clin Immunol 2001, 107:1034–1038.CrossRefPubMed
54.
Chetta A, Zanini A, Foresi A, D'Ippolito R, Tipa A, Castagnaro A, Baraldo S, Neri M, Saetta M, Olivieri D: Vascular endothelial growth factor and bronchial wall remodelling in asthma. Clin Exp Allergy 2005, 35:1437–1442.CrossRefPubMed
55.
Ferrara N, Gerber HP, LeCouter J: The biology of VEGF and its receptors. Nat Med 2003, 9:669–676.CrossRefPubMed
56.
O'Reilly MS, Bohem T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997, 88:277–285.CrossRefPubMed
57.
Lee KS, Min KH, Kim SR, Park SJ, Park HS, Jin GJ, Lee YC: Vascular endothelial growth factor modulates metalloproteinase-9 expression in asthma. Am J Respir Crit Care Med 2006, 174:161–170.CrossRefPubMed
58.
59.
Zanini A, Chetta A, Saetta M, Baraldo S, D'Ippolito R, Castagnaro A, Neri M, Olivieri D: Chymase-positive mast cells play a role in the vascular component of airway remodelling in asthma. J Allergy Clin Immunol 2007, 120:329–333.CrossRefPubMed
60.
Bosken CH, Wiggs BR, Paré PD, Hogg JC: Small airway dimensions in smokers with obstruction to airflow. Am Rev Respir Dis 1990, 142:563–570.CrossRefPubMed
61.
Zanini A, Chetta A, Nicolini G, Castagnetti C, D'Ippolito R, Neri M, Olivieri D: Vascular remodelling and inhaled beclomethasone dipropionate in COPD. Thorax 2009, 64:1019–1024.CrossRefPubMed
62.
Polosukhin VV, Lawson WE, Milstone AP, Egunova SM, Kulipanov AG, Tchuvakin SG, Massion PP, Balckwell TS: Association of progressive structural changes in the bronchial epithelium with subepithelial fibrous remodeling: a potential role for hypoxia. Virchows Arch 2007, 451:793–803.CrossRefPubMed
63.
Soltani A, Sohal S, Reid D, Muller HK, Weston S, Wood-Baker R, Walters EH: Inhaled corticosteroids in airway remodelling in COPD. Thorax 2009,64(Suppl 4):A55.
64.
Soltani A, Reid D, Sohal S, Muller HK, Weston S, Wood-Baker R, Walters EH: Vascular and basement membrane remodelling in smokers and COPD. Eur Respir J 2009, (Suppl 53):485.
65.
Kanzawa H, Asai K, Hirata K, Yoshikawa J: Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. Am J Med 2003, 114:354–358.CrossRef
66.
Kranenburg AR, de Boer WI, Alagappan VKT, Sterk PJ, Sharma HS: Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease. Thorax 2005, 60:106–113.CrossRefPubMedPubMedCentral
67.
Soldi R, Mitola S, Strasly M, Defilippi P, tarone G, Bussolino F: Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. EMBO J 1999, 18:882–892.CrossRefPubMedPubMedCentral
68.
Kranenburg AR, Willems-Widyastuti A, Mooi WJ, Saxena PR, Sterk PJ, de Boer WI, Sharma HS: Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1, FGF-2 and FGFR-1. J Pathol 2005, 206:28–38.CrossRefPubMed
69.
Kranenburg AR, Willems-Widyastuti A, Mooi WJ, Sterk PJ, Alagappan VKT, de Boer WI, Sharma HS: Enhanced bronchial expression of extracellular matrix proteins in chronic obstructive pulmonary disease. Am J Clin Pathol 2006, 126:725–735.CrossRefPubMed
70.
Maruotti N, Cantatore FP, Crivellato E, Vacca A, Ribatti D: Angiogenesis in rheumatoid arthritis. Histol Histopathol 2006, 21:557–566.PubMed
71.
Wilson JW, Kotsimbos T: Airway vascular remodelling in asthma. Curr Allergy Asthma Rep 2003, 3:153–158.CrossRefPubMed
72.
Wang L, McParland BE, Paré PD: The functional consequences of structural changes in airways. Chest 2003, 123:356S-362S.CrossRefPubMed
73.
74.
Feltis BN, Wignarajah D, Reid DW, Ward C, Harding R, Walters EH: Effects of inhaled fluticasone on angiogenesis and vascular endothelial growth factor in asthma. Thorax 2007, 62:314–319.CrossRefPubMed
75.
Orsida BE, Ward C, Li X, Bish R, Wilson J, Thien F, Walters EH: Effect of a long-acting β2-agonist over three months on airway wall vascular remodelling in asthma. Am J Respir Crit Care Med 2001, 164:117–121.CrossRefPubMed
76.
Reid DW, Ward C, Wang N, Zheng L, Bish R, Orsida BE, Walters EH: Possible anti-inflammatory effect of salmeterol against interleukin-8 and neutrophil activation in asthma in vivo. Eur Respir J 2003, 21:994–999.CrossRefPubMed
77.
Mendes ES, Campos MA, Hurtado A, Wanner A: Effect of montelukast and fluticasone propionate on airway mucosal blood flow in asthma. Am J Respir Crit Care Med 2004, 169:1131–1134.CrossRefPubMed
78.
Horn L, Sandler AB: Angiogenesis in the treatment of non-small cell lung cancer. Proc Am Thorac Soc 2009, 6:206–217.CrossRefPubMed
Metadata
Title
The role of the bronchial microvasculature in the airway remodelling in asthma and COPD
Authors
Andrea Zanini
Alfredo Chetta
Andrea S Imperatori
Antonio Spanevello
Dario Olivieri
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2010
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-11-132

Other articles of this Issue 1/2010

Respiratory Research 1/2010 Go to the issue

Research

Pulmonary hemodynamic responses to in utero ventilation in very immature fetal sheep

Research

Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study

Review

Involvement of microRNAs in physiological and pathological processes in the lung

Research

Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice

Research

Are exhaled nitric oxide measurements using the portable NIOX MINO repeatable?

Research

A prostacyclin analogue, iloprost, protects from bleomycin-induced pulmonary fibrosis in mice
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits