Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema
Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema
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DOI：
10.1164/ajrccm.163.3.2002117
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发表时间：
2001-03-01
影响因子：
24.7
通讯作者：
Voelkel, NF
中科院分区：
文献类型：
--
作者：
Kasahara, Y;Tuder, RM;Voelkel, NF
吸烟引起的肺气肿的特征是肺泡结构的丧失。我们推测肺泡的消失与肺间隔内皮细胞的凋亡和肺血管内皮细胞生长因子及其受体2的表达减少有关。用末端转移酶dUTP缺口末端标记法结合免疫组织化学方法，发现肺气肿肺泡间隔中TUNEL+间隔上皮细胞和内皮细胞/肺组织核酸(MUG，n=6)的数量(14.2±-2.0/MUG，n=6)明显高于正常肺(6.8+/-1.3/MUG，n=7)和原发性肺动脉高压肺(2.3+/-0.8/MUG，n=5)(P<；0.001)。细胞死亡事件在健康非吸烟者(7.4+/-1.9/杯)和吸烟者(5.7+/-0.7/杯)对照组之间无显著差异。用单链DNA和活性caspase-3免疫组织化学及DNA连接实验证实了TUNEL结果。肺气肿肺(n=12)与正常肺(n=11)相比，寡核小体长度DNA片段化水平增加。肺气肿组织中血管内皮生长因子、血管内皮生长因子R2蛋白和mRNA的表达均显著降低。我们认为，内皮细胞维持因子减少导致的上皮和内皮细胞肺泡间隔死亡可能是肺气肿发病机制的一部分。
Emphysema due to cigarette smoking is characterized by a loss of alveolar structures. We hypothesize that the disappearance of alveoli involves apoptosis of septal endothelial cells and a decreased expression of lung vascular endothelial growth factor (VEGF) and its receptor 2 (VEGF R2). By terminal transferase dUTP nick end labeling (TUNEL) in combination with immunohistochemistry, we found that the number of TUNEL+ septal epithelial and endothelial cells/lung tissue nucleic acid (mug) was increased in the alveolar septa of emphysema lungs (14.2 +/- 2.0/mug, n = 6) when compared with normal lungs (6.8 +/- 1.3/mug, n = 7) (p < 0.01) and with primary pulmonary hypertensive lungs (2.3 +/- 0.8/mug, n = 5) (p < 0.001). The cell death events were not significantly different between healthy nonsmoker (7.4 +/- 1.9/mug) and smoker (5.7 +/- 0.7/mug) control subjects. The TUNEL results were confirmed by single-stranded DNA and active caspase-3 immunohistochemistry, and by DNA ligation assay. Emphysema lungs (n = 12) had increased levels of oligonucleosomal-length DNA fragmentation when compared with normal lungs (n = 11). VEGF, VEGF R2 protein, and mRNA expression were significantly reduced in emphysema. We propose that epithelial and endothelial alveolar septal death due to a decrease of endothelial cell maintenance factors may be part of the pathogenesis of emphysema.