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.
Highlights
Several proangiogenic molecules have been implicated in the pathogenies of asthmatic inflammation and remodeling
Phenotypic heterogeneity of asthmatic patients Based on the American Thoracic Society (ATS) criteria 45 patients were diagnosed to have severe/refractory asthma (SRA) and the remaining 51 patients were assigned to the non-severe asthma group (Table 1)
The mean number of exacerbations was significantly higher in SRA group, and only patients belonging to this group reported interventions of emergency service and/or hospitalizations during preceding 12 months, despite significantly higher mean dose of inhaled corticosteroids and the fact that majority
Summary
Several 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 asth‐ matic patients and in healthy subjects (HS), and to refer the concentrations to both clinical and inflammatory markers of the disease severity. Not included in the definition, is another key feature of asthmatic airways and has been shown to correlate with the disease severity and contribute to the airway irreversibility [2]. The mechanisms associated with angiogenesis and airway remodeling are poorly understood but seem to be regulated by the balance between proangiogenic growth factors and angiostatic proteins [11]. In chronic inflammation associated with asthma the domination of proangiogenic factors and other mediators with proangiogenic properties have been observed [12]. Angiopoietins (Angiopoietin 1 and Makowska et al Allergy Asthma Clin Immunol (2016) 12:8
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