2nd Respiratory Medicine Department, University of Athens Medical School, 'Attikon' Hospital, Greece.
Allergy. 2012 Mar;67(3):396-402. doi: 10.1111/j.1398-9995.2011.02768.x. Epub 2012 Jan 9.
Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor.
We aimed to determine the levels of angiopoietins in sputum supernatants of patients with SRA and to investigate the possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling processes.
Thirty-eight patients with SRA, 35 patients with moderate asthma, and 20 healthy subjects were studied. All participants underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, Cys-LTs, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed.
Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly elevated in patients with SRA compared with patients with moderate asthma and control subjects [median, interquartile ranges: 30 (17-39) vs 7.5 (5-11) vs 4.7 (3.8-5.9) respectively, P < 0.001; and 506 (400-700) vs 190 (146-236) vs 96 (89-120) respectively, P < 0.001]. Regression analysis showed a significant positive association between Ang-2 and AVP index, MMP-2, Ang-1, and VEGF in SRA. A weak association was also observed between Ang-1 and sputum eosinophils% in SRA.
Our results indicate that both angiopoietins levels are higher in SRA compared with moderate asthma and healthy subjects. In SRA, Ang-2 is associated with mediators involved in both the inflammatory and the vascular remodeling processes.
气道和血管重塑可能在严重难治性哮喘（SRA）的临床严重程度中起重要作用。血管生成素-1（Ang-1）是通过建立血管完整性来实现血管生成的重要介质，而血管生成素-2（Ang-2）则作为其天然抑制剂。
我们旨在确定 SRA 患者痰上清液中血管生成素的水平，并研究其与参与炎症和血管重塑过程的介质和细胞的可能相关性。
研究了 38 例 SRA 患者、35 例中度哮喘患者和 20 例健康对照者。所有参与者均进行了肺功能测试、支气管高反应性评估和痰诱导，以进行细胞计数鉴定以及测量上清液中 Ang-1、Ang-2、VEGF、TGF-β1、Cys-LTs、MMP-2、IL-13、ECP 和 IL-8。还评估了气道血管通透性（AVP）指数。
与中度哮喘患者和对照组相比，SRA 患者的 Ang-1（ng/ml）和 Ang-2（pg/ml）水平显著升高[中位数，四分位间距：30（17-39）比 7.5（5-11）比 4.7（3.8-5.9），P<0.001；506（400-700）比 190（146-236）比 96（89-120），P<0.001]。回归分析显示，SRA 中 Ang-2 与 AVP 指数、MMP-2、Ang-1 和 VEGF 呈显著正相关。SRA 中还观察到 Ang-1 与痰嗜酸性粒细胞%之间存在弱相关性。
我们的结果表明，与中度哮喘和健康对照组相比，SRA 患者的两种血管生成素水平均较高。在 SRA 中，Ang-2 与参与炎症和血管重塑过程的介质相关。
