Makowska Joanna S, Cieślak Małgorzata, Jarzębska Marzanna, Lewandowska-Polak Anna, Kowalski Marek L
Department of Rheumatology, Chair of Clinical Immunology and Microbiology, Healthy Aging Research Center, Medical University of Lodz, 251 Pomorska Str, 92-213 Lodz, Poland.
Department of Immunology, Rheumatology and Allergy, Medical University of Lodz, Lodz, Poland.
Allergy Asthma Clin Immunol. 2016 Mar 1;12:8. doi: 10.1186/s13223-016-0112-6. eCollection 2016.
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 asthmatic patients and in healthy subjects (HS), and to refer the concentrations to both clinical and inflammatory markers of the disease severity.
Serum 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.
The 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).
Angiopoietin-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.
多种促血管生成分子与哮喘炎症和重塑的发病机制有关。本研究旨在比较哮喘患者和健康受试者血清中促血管生成因子的浓度，并将这些浓度与疾病严重程度的临床及炎症标志物相关联。
收集45例重度/难治性哮喘（SRA）患者和51例非重度哮喘（nSA）患者的血清。对照组包括30名健康受试者。采用酶联免疫吸附测定法评估血清中血管生成素-1、血管生成素-2、血管内皮生长因子（VEGF）和骨桥蛋白的浓度。
与健康受试者相比，哮喘患者（n = 94）血清中血管生成素-1（68.8 ± 2.7 vs 56.4 ± 9.3 ng/ml；p < 0.05）、血管生成素-2（4.9 ± 0.35 vs 1.38 ± 0.14 ng/ml；p < 0.0001）和VEGF水平显著升高（255 ± 45.4 vs 424.5 ± 27.8 pg/ml；p < 0.01）。与nSA患者相比，SRA患者血清中血管生成素-2的平均水平显著更高（6.04 ± 0.46 vs 3.84 ± 0.43；p < 0.001）。血管生成素-2血清水平与呼吸功能及哮喘严重程度参数相关：前12个月哮喘发作的平均次数（R = 0.21；p < 0.05）、因严重哮喘发作的急诊就诊平均次数（R = 0.24；p < 0.04）、住院平均次数（R = 0.21；p < 0.05）或患者吸入糖皮质激素的剂量（R = 0.36；p < 0.001）。
血管生成素-2似乎是一种关键的促血管生成细胞因子，在以反复发作为特征的SRA患者中过度产生，且血管生成素-2血清水平可作为重度哮喘的生物标志物。
