The Division of Pulmonary Medicine, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA.
Pediatr Pulmonol. 2011 Jul;46(7):683-7. doi: 10.1002/ppul.21428. Epub 2011 Mar 1.
Angiogenesis is an important mechanism of airway remodeling in lung disease. We previously demonstrated that serum vascular endothelial growth factor (VEGF) is elevated in cystic fibrosis (CF) patients and declines with therapy for pulmonary exacerbation. We hypothesized that VEGF is elevated early in the course of CF and is associated with markers of tissue hypoxia. A prospective, single-visit evaluation of thirty stable infants and children with CF was performed. Serum was analyzed for VEGF and for other markers of tissue hypoxia (erythropoietin (EPO), insulin-like growth factor binding protein-1 (IGFBP-1)) and for inflammatory mediators (IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha (TNFα)) using Meso Scale multi-spot serum immunoassays. Measurements were correlated between assay groups; and with age in months and pulmonary function (FEV0.5 or FEV1). VEGF, EPO, TNFα and IL-8 were elevated compared to published normative values. VEGF levels were not significantly correlated with any inflammatory mediators. However, VEGF correlated with EPO (r=0.505; P<0.05). There was no correlation between lung function and markers of inflammation or tissue hypoxia. VEGF is elevated in young, stable infants and children suggesting angiogenesis as a contributing mechanism for early lung disease in CF. VEGF elevation does not show significant correlation with inflammatory mediators known to be increased in CF, but is significantly correlated with EPO levels. We propose that VEGF elevation and angiogenesis contribute to early lung disease and may result from a direct tissue hypoxia pathway in CF.
血管生成是肺部疾病气道重塑的重要机制。我们之前的研究表明，囊性纤维化（CF）患者的血清血管内皮生长因子（VEGF）升高，并随着肺部感染的治疗而下降。我们假设 VEGF 在 CF 的早期就升高，并与组织缺氧的标志物有关。我们对 30 例稳定期 CF 婴儿和儿童进行了前瞻性、单次就诊评估。使用 Meso Scale 多斑点血清免疫分析方法检测血清 VEGF 和其他组织缺氧标志物（促红细胞生成素（EPO）、胰岛素样生长因子结合蛋白-1（IGFBP-1））和炎症介质（IL-1β、IL-6、IL-8 和肿瘤坏死因子-α（TNFα））。在测定组之间进行了测量相关性；并与月龄和肺功能（FEV0.5 或 FEV1）进行了相关性。与已发表的正常参考值相比，VEGF、EPO、TNFα 和 IL-8 均升高。VEGF 水平与任何炎症介质均无显著相关性。然而，VEGF 与 EPO 呈正相关（r=0.505；P<0.05）。肺功能与炎症或组织缺氧标志物之间无相关性。VEGF 在年轻、稳定的婴儿和儿童中升高，提示血管生成是 CF 早期肺部疾病的一个致病机制。VEGF 升高与 CF 中已知升高的炎症介质无显著相关性，但与 EPO 水平显著相关。我们提出，VEGF 升高和血管生成导致 CF 早期肺部疾病，可能是 CF 中直接的组织缺氧途径所致。
