Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma
Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma
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DOI：
10.1111/j.1365-2222.2005.02360.x
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Olivieri, D
中科院分区：
文献类型：
--
作者：
Chetta, A;Zanini, A;Olivieri, D
背景 越来越多的体外证据支持血管内皮生长因子 (VEGF) 的作用，血管内皮生长因子 (VEGF) 是血管生成的主要调节剂，是与新生血管形成相关的纤维化介质。 目的 我们测试了 VEGF 参与哮喘患者气道粘膜血管分布增加和上皮下纤维化的假设。 方法 对 24 名哮喘患者和 8 名健康对照者进行了支气管活检。采用计算机图像分析，使用针对 VEGF(+) 细胞的单克隆抗体和 IV 型胶原进行免疫染色，以勾画基底膜厚度，并使用类胰蛋白酶和 EG2 分别识别肥大细胞和嗜酸性粒细胞。 结果 哮喘患者中 VEGF(+) 细胞 (P < 0.05)、肥大细胞和 EG2(+) 细胞 (均 P < 0.01) 计数高于对照组。哮喘患者的血管数量、固有层血管面积和基底膜厚度均显着高于健康志愿者（P < 0.01）。此外，在哮喘患者中，VEGF(+)细胞的数量与血管数量(P < 0.01)、肥大细胞(P < 0.01)和基底膜厚度(P < 0.01)显着相关。共定位研究还表明，肥大细胞是 VEGF 的相关细胞来源。高剂量吸入丙酸氟替卡松显着减少哮喘患者亚组中的 VEGF(+) 细胞 (P < 0.05)、血管数量 (P < 0.05)、血管面积 (P < 0.05) 和基底膜厚度 (P < 0.05)。 结论 本研究表明 VEGF 除了参与气道重塑的血管成分外，还可能在基底膜增厚中发挥作用。在哮喘中。
Background There is increasing in vitro evidence to support a role for vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, as a mediator of fibrosis associated with neovascularization.Objective We tested the hypothesis that VEGF is involved both in increased airway mucosal vascularity and in the subepithelial fibrosis of asthmatic patients.Methods Bronchial biopsies were performed in 24 asthmatic patients and eight healthy controls. Immunostaining, using computerized image analysis, was performed using monoclonal antibodies against VEGF(+) cells, type IV collagen, to outline the basement membrane thickness, and tryptase and EG2, to identify mast cells and eosinophils, respectively.Results The counts of VEGF(+) cells (P < 0.05), mast cells and EG2(+) cells (both P < 0.01) were higher in asthmatics than in controls. The number of vessels, the vascular area in the lamina propria, and the basement membrane thickness were significantly higher in asthmatics than in healthy volunteers (P < 0.01). Moreover, in asthmatic patients, the number of VEGF(+) cells was significantly related to the number of vessels (P < 0.01), to mast cells (P < 0.01) and to basement membrane thickness (P < 0.01). A colocalization study also revealed that mast cells were a relevant cellular source of VEGF. High doses of inhaled fluticasone propionate significantly reduced VEGF(+) cells (P < 0.05), vessel number (P < 0.05), vascular area (P < 0.05) and basement membrane thickness (P < 0.05) in a subgroup of asthmatic patients.Conclusions This study shows that VEGF, in addition to being involved in the vascular component of airway remodelling, may play a role in the thickening of the basement membrane in asthma.