Endoglin (CD105) up-regulation in pulmonary microvasculature of ventilated preterm infants
Endoglin (CD105) up-regulation in pulmonary microvasculature of ventilated preterm infants
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DOI：
10.1164/rccm.200608-1240oc
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发表时间：
2008-07-15
影响因子：
24.7
通讯作者：
Mao, Quanfu
中科院分区：
文献类型：
--
作者：
De Paepe, Monique E.;Patel, Chintan;Mao, Quanfu
原理暴露在机械通风和氧气环境中的早产儿有患支气管肺发育不良(BIRD)的风险，这是一种以肺泡发育受阻为特征的多因素慢性肺部疾病。研究已经描述了BPD的微血管发育中断，其特征是原始的血管构筑模式使人想起肺发育的管状/囊状阶段。目的：Endoglin(CD105)是一种低氧诱导的转化生长因子-β辅助受体，在多种肿瘤和非肿瘤条件下被认为是血管生成的重要调节因子。本研究的目的是研究Endoglin和其他血管生成相关因子在呼吸机治疗的早产儿肺组织中的表达。方法：对短期和长期呼吸机治疗的早产儿死后肺组织中Endoglin蛋白和mRNA的表达进行研究。测量和主要结果：短期机械通气的早产儿肺组织中endoglin基因和蛋白水平显著上调，免疫定位于微血管。长期使用呼吸机的婴幼儿肺组织中有相似但更具变异性的内源性激素上调。与年龄匹配的非机械通气组相比，机械通气组肺组织血管内皮生长因子、血管生成素-1及其受体的表达水平显著降低。结论：BPD患者肺组织中血管内皮生长因子、血管生成素-1的表达水平与传统的血管生成因子(血管内皮生长因子、血管生成素-1)向Endoglin等替代性调节因子的转变有关，这可能是BPD相关微血管生成障碍的原因之一。
Rationale Preterm infants exposed to mechanical ventilation and oxygen are at risk for bronchopulmonary dysplasia (BIRD), a multifactorial chronic lung disorder characterized by arrested alveolar development. Studies have described disruption of microvascular development in BPD, characterized by primitive angioarchitectural patterns reminiscent of the canalicular/saccular stages of lung development. The molecular regulation of this BPD-associated dysangiogenesis remains undetermined.Objectives: Endoglin (CD105), a hypoxia-inducible transforming growth factor-beta coreceptor, has been implicated as an important regulator of angiogenesis in various neoplastic and nonneoplastic conditions. The aim of this study was to investigate the expression of endoglin and other angiogenesis-related factors in ventilated preterm human lungs.Methods: We have studied endoglin protein and mRNA expression in postmortem lungs of short-term and long-term ventilated preterm infants. Control subjects were age-matched infants who had lived for less than 1 hour.Measurements and Main Results: Lungs of short-term ventilated preterm infants showed significant upregulation of endoglin mRNA and protein levels, immunolocalized to the microvasculature. Similar but more variable endoglin upregulation was noted in lungs of longterm ventilated infants with BIRD. The mRNA levels of vascular endothelial growth factor, angiopoietin-1, and their respective receptors were significantly lower in ventilated lungs than in age-matched nonventilated control lungs.Conclusions: BIRD is associated with a shift from traditional angiogenic growth factors (vascular endothelial growth factor, angiopoietin-1) to alternative regulators such as endoglin, which may contribute to BPD-associated microvascular dysangiogenesis.