Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury -: Evidence that angiogenesis participates in alveolarization
Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury -: Evidence that angiogenesis participates in alveolarization
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DOI：
10.1161/circulationaha.105.541524
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发表时间：
2005-10-18
期刊：
影响因子：
37.8
通讯作者：
Archer, SL
中科院分区：
文献类型：
--
作者：
Thébaud, B;Ladha, F;Archer, SL
背景-支气管肺发育不良（BPD）和肺气肿，这两个重要的全球性健康问题，其特征是肺泡的损失。血管内皮生长因子（VEGF）是一种营养因子所需的内皮细胞的生存和大量表达在lung.Methods和结果-我们报告，VEGF阻断降低肺VEGF和VEGF受体2（VEGFR-2）的表达在新生大鼠和损害肺泡发育，导致肺泡简化和肺毛细血管的损失，模仿BPD。在新生大鼠高氧诱导的BPD中，空气空间扩大和肺毛细血管损失与肺VEGF和VEGFR-2表达降低相关。出生后肺内腺病毒介导的VEGF基因治疗改善了这种不可逆肺损伤模型的存活率，促进了肺毛细血管形成，并保护了肺泡发育。结合VEGF和促血管生成素-1基因转移成熟的新的脉管系统，减少血管渗漏中看到的VEGF诱导的capillars.Conclusions -这些研究结果强调了脉管系统的重要性，在传统上被认为是一种气道疾病和开放的新的治疗途径，肺部疾病的特点是通过调节血管生成生长因子的肺泡不可逆的损失。
Background - Bronchopulmonary dysplasia (BPD) and pulmonary emphysema, both significant global health problems, are characterized by a loss of alveoli. Vascular endothelial growth factor ( VEGF) is a trophic factor required for endothelial cell survival and is abundantly expressed in the lung.Methods and Results - We report that VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries, mimicking BPD. In hyperoxia-induced BPD in newborn rats, air space enlargement and loss of lung capillaries are associated with decreased lung VEGF and VEGFR-2 expression. Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development in this model of irreversible lung injury. Combined VEGF and angiopoietin-1 gene transfer matures the new vasculature, reducing the vascular leakage seen in VEGF-induced capillaries.Conclusions - These findings underscore the importance of the vasculature in what is traditionally thought of as an airway disease and open new therapeutic avenues for lung diseases characterized by irreversible loss of alveoli through the modulation of angiogenic growth factors.