内皮向间充质转化是吸烟者和早期慢性阻塞性肺疾病（COPD）患者中的一个活跃过程，它会导致肺动脉病变。

Endothelial to mesenchymal transition is an active process in smokers and patients with early COPD contributing to pulmonary arterial pathology.

作者信息

Bhattarai Prem, Lu Wenying, Hardikar Ashutosh, Dey Surajit, Gaikwad Archana Vijay, Shahzad Affan Mahmood, Chia Collin, Williams Andrew, Singhera Gurpreet Kaur, Hackett Tillie-Louise, Eapen Mathew Suji, Sohal Sukhwinder Singh

机构信息

Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.

Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia.

出版信息

ERJ Open Res. 2024 Feb 12;10(1). doi: 10.1183/23120541.00767-2023. eCollection 2024 Jan.

BACKGROUND

We have previously reported pulmonary arterial remodelling in smokers and patients with early COPD, which can be attributed to endothelial to mesenchymal transition (EndMT). In this study, we aimed to evaluate if EndMT is an active mechanism in smokers and COPD.

METHODS

Immunohistochemical staining for the EndMT biomarkers CD31, N-cadherin, vimentin and S100A4 was done on lung resection tissue from 49 subjects. These comprised 15 nonsmoker controls (NC), six normal lung function smokers (NLFS), nine patients with small airway disease (SAD), nine current smokers with mild-moderate COPD (COPD-CS) and 10 ex-smokers with COPD (COPD-ES). Pulmonary arteries were analysed using Image ProPlus software v7.0.

RESULTS

We noted reduced junctional CD31 endothelial cells (p<0.05) in the intimal layer of all smoking groups compared to NC. We also observed increased abundance of the mesenchymal markers N-cadherin (p<0.05) and vimentin (p<0.001) in all smoking groups and across all arterial sizes NC, except for N-cadherin in large arteries in COPD-CS. The abundance of S100A4 correlated with arterial thickness (small: r=0.29, p=0.05; medium: r=0.33, p=0.03; large: r=0.35, p=0.02). Vimentin in the small arterial wall negatively correlated with forced expiratory volume in 1 s/forced vital capacity (r= -0.35, p=0.02) and forced expiratory flow rate at 25-75% of forced vital capacity (r= -0.34, p=0.03), while increased cytoplasmic CD31 abundance in the intimal layer of medium and large arteries negatively correlated with predicted diffusing capacity of the lung for carbon monoxide (medium: r= -0.35, p=0.04; large: r= -0.39, p=0.03).

CONCLUSION

This is the first study showing the acquisition of mesenchymal traits by pulmonary endothelial cells from NLFS, SAD and mild-moderate COPD patients through EndMT. This informs on the potential early origins of pulmonary hypertension in smokers and patients with early COPD.

背景

我们之前报道过吸烟者和早期慢性阻塞性肺疾病（COPD）患者存在肺动脉重塑，这可归因于内皮-间质转化（EndMT）。在本研究中，我们旨在评估EndMT在吸烟者和COPD患者中是否为一种活跃机制。

方法

对49名受试者的肺切除组织进行EndMT生物标志物CD31、N-钙黏蛋白、波形蛋白和S100A4的免疫组织化学染色。这些受试者包括15名非吸烟对照者（NC）、6名肺功能正常的吸烟者（NLFS）、9名小气道疾病患者（SAD）、9名轻度至中度COPD现吸烟者（COPD-CS）和10名COPD戒烟者（COPD-ES）。使用Image ProPlus软件v7.0对肺动脉进行分析。

结果

我们注意到，与NC相比，所有吸烟组内膜层的连接性CD31内皮细胞减少（p<0.05）。我们还观察到，除了COPD-CS组大动脉中的N-钙黏蛋白外，所有吸烟组以及所有动脉大小的NC组中，间充质标志物N-钙黏蛋白（p<0.05）和波形蛋白（p<0.001）的丰度增加。S100A4的丰度与动脉厚度相关（小动脉：r=0.29，p=0.05；中动脉：r=0.33，p=0.03；大动脉：r=0.35，p=0.02）。小动脉壁中的波形蛋白与1秒用力呼气量/用力肺活量（r=-0.35，p=0.02）以及用力肺活量25%-75%时的用力呼气流量（r=-0.34，p=0.03）呈负相关，而中动脉和大动脉内膜层中细胞质CD31丰度增加与预测的肺一氧化碳弥散量呈负相关（中动脉：r=-0.35，p=0.04；大动脉：r=-0.39，p=0.03）。