Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure. Microvasculature dysfunction is associated with COPD/emphysema. However, it is not known if abnormal endothelium drives COPD/emphysema pathology and/or if correcting endothelial dysfunction has therapeutic potential. Here, we show the centrality of endothelial cells to the pathogenesis of COPD/emphysema in human tissue and using an elastase-induced murine model of emphysema. Airspace disease showed significant endothelial cell loss, and transcriptional profiling suggested an apoptotic, angiogenic, and inflammatory state. This alveolar destruction was rescued by intravenous delivery of healthy lung endothelial cells. Leucine-rich α-2-glycoprotein-1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression. Hence, targeting endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent strategies of immense potential for the treatment of COPD/emphysema.

中文翻译：

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通过恢复肺内皮细胞逆转肺气肿

慢性阻塞性肺病 (COPD) 的特征是气道炎症和气腔扩大（肺气肿），导致气流阻塞和最终的呼吸衰竭。微血管功能障碍与 COPD/肺气肿有关。然而，尚不清楚异常内皮是否会导致 COPD/肺气肿病理和/或纠正内皮功能障碍是否具有治疗潜力。在这里，我们展示了内皮细胞对人体组织中 COPD/肺气肿发病机制的中心作用，并使用弹性蛋白酶诱导的肺气肿小鼠模型。气腔疾病显示出显着的内皮细胞丢失，转录谱表明存在凋亡、血管生成和炎症状态。通过静脉内输送健康的肺内皮细胞来挽救这种肺泡破坏。来自内皮细胞的Lrg1挽救了血管稀疏和肺泡退化。因此，通过再生方法和/或抑制 LRG1 途径靶向内皮细胞生物学可能代表治疗 COPD/肺气肿的巨大潜力的策略。