title: Expression of vascular remodelling markers in relation to bradykinin receptors in asthma and COPD.
abstract: BACKGROUND
  Vascular remodelling plays a central role in asthma and chronic obstructive pulmonary disease (COPD). Bradykinin (BK) is a vasoactive proinflammatory peptide mediating acute responses in asthma. We investigated the role of angiogenic factors in relation to BK receptors in asthma and COPD.
  
  
  METHODS
  Bronchial biopsies from 33 patients with COPD, 24 old (≥50 years) patients with (≥50 years) asthma, 18 old control smokers, 11 old control non-smokers, 15 young (≤40yrs) patients with (≤40 years) asthma and 10 young control non-smokers were immunostained for CD31, vascular endothelial growth factor-A (VEGF-A), angiogenin and BK receptors (B2R and B1R). Fibroblast and endothelial co-localisation of relevant molecules were performed by immunofluorescence. BK-induced VEGF-A and angiogenin release was studied (ELISA) in bronchial fibroblasts from subjects with asthma and COPD.
  
  
  RESULTS
  In bronchial lamina propria of old patients with asthma, CD31 and VEGF-A(+) cell numbers were higher than old control non-smokers (p<0.05). Angiogenin(+), B2R(+) and B1R(+) cell numbers in old patients with asthma were higher than in old control non-smokers, control smokers and patients with COPD (p<0.01). Angiogenin(+) cell numbers were higher in patients with COPD than both old control groups (p<0.05). In all patients with asthma the number of B2R(+) cells was positively related to the numbers of B1R(+) (rs=0.43), angiogenin(+) (rs=0.42) and CD31 cells (rs=0.46) (p<0.01). Angiogenin(+) cell numbers were negatively related to forced expiratory volume in 1 s (rs=-0.415, p=0.008). Double immunofluorescence revealed that CD31 cells of capillary vessels coexpressed B2R and that fibroblasts coexpressed B2R, VEGF-A and angiogenin. BK (10(-6)M) induced significant angiogenin release in fibroblasts from asthma and to a lesser extent in COPD.
  
  
  CONCLUSIONS
  Unlike COPD, this study suggests the involvement of BK receptors in bronchial vascular remodelling in asthma.
authors.affiliation: Division of Respiratory Disease, Department of Clinical and Biological Sciences, A.O.U. San Luigi Hospital, University of Torino, Orbassano, Torino, Italy. fabioluigimassimo.ricciardolo@unito.it
authors.forename: Fabio L M
authors.initials: FL
authors.lastname: Ricciardolo
authors.forename: Federica
authors.initials: F
authors.lastname: Sabatini
authors.forename: Valentina
authors.initials: V
authors.lastname: Sorbello
authors.forename: Sabrina
authors.initials: S
authors.lastname: Benedetto
authors.forename: Ilaria
authors.initials: I
authors.lastname: Defilippi
authors.forename: Loredana
authors.initials: L
authors.lastname: Petecchia
authors.forename: Cesare
authors.initials: C
authors.lastname: Usai
authors.forename: Isabella
authors.initials: I
authors.lastname: Gnemmi
authors.forename: Bruno
authors.initials: B
authors.lastname: Balbi
authors.forename: Virginia
authors.initials: V
authors.lastname: De Rose
authors.forename: Nick H T
authors.initials: NH
authors.lastname: Ten Hacken
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: Antonino
authors.initials: A
authors.lastname: Di Stefano
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000367:Age Factors; D000368:Aged; D001249:Asthma / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000098:blood supply* / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D042783:Endothelial Cells; D005260:Female; D005347:Fibroblasts; D006801:Humans; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D012907:Smoking / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D042461:Vascular Endothelial Growth Factor A; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: Asthma Mechanisms; COPD Pathology