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 nonsmokers, 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 (10-6M) 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.