Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia
Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia
复制标题
DOI：
10.1164/ajrccm.164.10.2101140
复制
发表时间：
2001-11-15
影响因子：
24.7
通讯作者：
Maniscalco, WM
中科院分区：
文献类型：
--
作者：
Bhatt, AJ;Pryhuber, GS;Maniscalco, WM
肺血管异常可能是支气管肺发育不良（BPD）的重要组成部分。我们检测了人类婴儿肺内皮细胞标志物PECAM-1和血管生成因子及其受体。在死亡后6小时左右前瞻性采集肺标本。右中肺叶膨胀固定，右下肺叶部分瞬间冻结。我们比较了死于BIRD的婴儿肺（n = 5）和死于非肺原因的婴儿肺（n = 5）。BPD组明显更早产，使用呼吸机和补充氧气支持的天数更长，但在受孕后死亡的年龄与对照组相似。BPD组PECAM-1蛋白和mRNA水平降低。PECAM-1免疫组化显示BPD组肺泡毛细血管染色强度降低，分布异常。畸形毛细血管常见于增厚的肺泡间隔内部。与未患BPD的婴儿相比，BPD组血管内皮生长因子（VEGF） mRNA和VEGF免疫染色降低。BPD组血管生成受体Flt-1和TIE-2的信息减少。我们的结论是，死于BPD的婴儿有异常的肺泡微血管，血管生成生长因子及其受体的表达紊乱可能导致这些异常。
An abnormal pulmonary vasculature may be an important component of bronchopulmonary dysplasia (BPD). We examined human infant lung for the endothelial cell marker PECAM-1 and for angiogenic factors and their receptors. Lung specimens were collected prospectively at similar to 6 h after death. The right middle lobe was inflation fixed and part of the right lower lobe was flash frozen. We compared lungs from infants dying with BIRD (n = 5) with lungs from infants dying from nonpulmonary causes (n = 5). The BPD group was significantly more premature and had more days of ventilator and supplemental oxygen support, but died at a postconceptional age similar to control infants. PECAM-1 protein and mRNA were decreased in the BPD group. PECAM-1 immunohistochemistry showed the BPD group had decreased staining intensity and abnormal distribution of alveolar capillaries. The dysmorphic capillaries were frequently in the interior of thickened alveolar septa. The BPD group had decreased vascular endothelial growth factor (VEGF) mRNA and decreased VEGF immunostaining, compared with infants without BPD. Messages for the angiogenic receptors Flt-1 and TIE-2 were decreased in the BPD group. We conclude that infants dying with BPD have abnormal alveolar microvessels and that disordered expression of angiogenic growth factors and their receptors may contribute to these abnormalities.