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: Fabio L M Ricciardolo, Federica Sabatini, Valentina Sorbello, Sabrina Benedetto, Ilaria Defilippi, Loredana Petecchia, Cesare Usai, Isabella Gnemmi, Bruno Balbi, Virginia De Rose, Nick H T Ten Hacken, Dirkje S Postma, Wim Timens, Antonino Di Stefano
• Journal: Thorax (Thorax) Vol. 68 Issue 9 Pg. 803-11 (Sep 2013) ISSN: 1468-3296 [Electronic] England
• PMID: 23739138 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Platelet Endothelial Cell Adhesion Molecule-1
• Receptor, Bradykinin B1
• Receptor, Bradykinin B2
• Vascular Endothelial Growth Factor A
• angiogenin
• Ribonuclease, Pancreatic

Topics

• Adaptation, Physiological
• Adult
• Age Factors
• Aged
• Asthma (metabolism)
• Biomarkers (metabolism)
• Bronchi (blood supply, metabolism)
• Capillaries (metabolism, physiopathology)
• Case-Control Studies
• Endothelial Cells
• Female
• Fibroblasts
• Humans
• Male
• Middle Aged
• Platelet Endothelial Cell Adhesion Molecule-1 (metabolism)
• Pulmonary Disease, Chronic Obstructive (metabolism)
• Receptor, Bradykinin B1 (metabolism)
• Receptor, Bradykinin B2 (metabolism)
• Ribonuclease, Pancreatic (metabolism)
• Smoking (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)
• Young Adult