Angiopoietin-2 concentration in serum is associated with severe asthma phenotype

Abstract

BackgroundSeveral proangiogenic molecules have been implicated in the pathogenies of asthmatic inflammation and remodeling. The aim of the study was to compare the concentration of proangiogenic factors in the sera of asthmatic patients and in healthy subjects (HS), and to refer the concentrations to both clinical and inflammatory markers of the disease severity.MethodsSerum was collected from 45 patients with severe/refractory asthma (SRA) and 51 patients with non-severe asthma (nSA). The control group included 30 HS. Serum concentrations of Angiopoietin-1, Angiopoietin-2, vascular endothelial growth factor (VEGF) and osteopontin were assessed by the enzyme-linked immunosorbent assay.ResultsThe levels of Angiopoietin-1 (68.8 ± 2.7 vs 56.4 ± 9.3 ng/ml; p < 0.05), Angiopoietin-2 (4.9 ± 0.35 vs 1.38 ± 0.14 ng/ml; p < 0.0001) and VEGF were significantly higher in asthmatic patients (n = 94) as compared to HS (255 ± 45.4 vs 424.5 ± 27.8 pg/ml; p < 0.01). The mean serum level of Angiopoietin-2 was found to be significantly higher in patients with SRA as compared to nSA patients (6.04 ± 0.46 vs 3.84 ± 0.43; p < 0.001). Angiopoietin-2 serum level correlated with respiratory function and with parameters of asthma severity: the mean number of asthma exacerbations in the preceding 12 months (R = 0.21; p < 0.05), mean number of emergency visits due to severe asthma exacerbation (R = 0.24; p < 0.04) and mean number of hospitalizations (R = 0.21; p < 0.05) or dose of inhaled glucocorticosteroids taken by the patients (R = 0.36; p < 0.001).ConclusionAngiopoietin-2 seems to be a crucial proangiogenic cytokine overproduced in patients with SRA characterized by repeated exacerbations and Angiopoietin-2 serum levels can serve as a biomarker of severe asthma.

Serum angiopoietin‐2 level as a novel biomarker in atopic dermatitis

“…Bourdeau et al hypothesized that atopic reaction to a mouse model was driven by deregulation of the Tie‐2 signaling pathway and that increased Ang‐2 levels can aggravate it and reverse by Ang‐1 overexpression. Increased Ang‐2 seems to be a crucial proangiogenic cytokine in patients with asthma characterized by repeated exacerbations and Ang‐2 serum levels (4.9 ± 0.35 vs. 1.38 ± 0.14 ng/ml; P < 0.0001), and can serve as a biomarker of severe asthma . Also, Lee et al found that plasma Ang‐2 levels were 23.96–1.38 pg/mg in patients with bronchial asthma compared with 36.8–4.46 pg/mg in healthy controls ( P = 0.010), and circulating angiopoietin could be a useful marker for asthma exacerbation.…”

The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD)

“…However, only serum Ang-2 appears to be related to disease severity and is higher in refractory asthma cases. Serum Ang-2 (but not Ang-1) also correlates with parameters of severe asthma including number of exacerbations, emergency medical trips and number of hospitalizations [122]. Serum Ang-2 is positively correlated with exercise-induced bronchoconstriction whereas Ang-1 does not show this association.…”

Targeting the Angiopoietin/Tie Pathway: Prospects for Treatment of Retinal and Respiratory Disorders

“…Serum Ang1 levels and Ang1/Ang2 ratio were decreased in asthmatic children, with Ang2 serum levels remaining stable [ 188 ]. However, in adults, serum Ang1 levels were increased, while changes of Ang2 serum levels were not consistent in asthmatic conditions [ 189 , 190 ]. In an ovalbumin asthma mouse model, Ang1 levels were decreased, similarly to Tie2 activation, and its administration ameliorated the inflammatory response [ 191 ].…”