Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
Respir Res. 2019 Apr 16;20(1):74. doi: 10.1186/s12931-019-1024-z.
BACKGROUND: Pulmonary vascular abnormalities are a characteristic feature of chronic obstructive pulmonary disease (COPD). Cigarette smoking is the most important risk factor for COPD. It is believed that its constant exposure triggers endothelial cell damage and vascular remodelling. Under pathological conditions, progenitor cells (PCs) are mobilized from the bone marrow and recruited to sites of vascular injury. The aim of the study was to investigate whether in COPD the number of circulating PCs is related to the presence of bone marrow-derived cells in pulmonary arteries and the association of these phenomena to both systemic and pulmonary endothelial dysfunction. METHODS: Thirty-nine subjects, 25 with COPD, undergoing pulmonary resection because of a localized carcinoma, were included. The number of circulating PCs was assessed by flow cytometry using a triple combination of antibodies against CD45, CD133 and CD34. Infiltrating CD45 cells were identified by immunohistochemistry in pulmonary arteries. Endothelial function in systemic and pulmonary arteries was measured by flow-mediated dilation and adenosine diphosphate-induced vasodilation, respectively. RESULTS: COPD patients had reduced numbers of circulating PCs (p < 0.05) and increased numbers of CD45 cells (< 0.05) in the pulmonary arterial wall than non-COPD subjects, being both findings inversely correlated (r = - 0.35, p < 0.05). In pulmonary arteries, the number of CD45 cells correlated with the severity of vascular remodelling (r = 0.4, p = 0.01) and the endothelium-dependent vasodilation (r = - 0.3, p = 0.05). Systemic endothelial function was unrelated to the number of circulating PCs and changes in pulmonary vessels. CONCLUSION: In COPD, the decrease of circulating PCs is associated with their recruitment in pulmonary arteries, which in turn is associated with endothelial dysfunction and vessel remodelling, suggesting a mechanistic link between these phenomena. Our findings are consistent with the notion of an imbalance between endothelial damage and repair capacity in the pathogenesis of pulmonary vascular abnormalities in COPD.
背景：肺血管异常是慢性阻塞性肺疾病（COPD）的一个特征。吸烟是 COPD 的最重要危险因素。据信，它的持续暴露会引发内皮细胞损伤和血管重塑。在病理条件下，祖细胞（PCs）从骨髓动员并募集到血管损伤部位。本研究旨在探讨 COPD 患者循环 PCs 的数量是否与肺小动脉中骨髓源性细胞的存在有关，以及这些现象与全身和肺内皮功能障碍的关系。 方法：纳入 39 名患者，25 名 COPD 患者因局限性癌行肺切除术。通过流式细胞术使用针对 CD45、CD133 和 CD34 的三重组合抗体评估循环 PCs 的数量。通过免疫组织化学鉴定肺小动脉中的浸润性 CD45 细胞。通过血流介导的扩张和腺苷二磷酸诱导的血管扩张分别测量全身和肺小动脉的内皮功能。 结果：与非 COPD 患者相比，COPD 患者的循环 PCs 数量减少（p < 0.05），肺小动脉壁中的 CD45 细胞数量增加（p < 0.05），两者呈负相关（r = -0.35，p < 0.05）。在肺小动脉中，CD45 细胞的数量与血管重塑的严重程度相关（r = 0.4，p = 0.01）和内皮依赖性血管扩张相关（r = -0.3，p = 0.05）。全身内皮功能与循环 PCs 的数量和肺血管的变化无关。 结论：在 COPD 中，循环 PCs 的减少与它们在肺小动脉中的募集有关，而后者又与内皮功能障碍和血管重塑有关，这表明这些现象之间存在机制联系。我们的发现与 COPD 中肺血管异常发病机制中内皮损伤和修复能力失衡的观点一致。
Am J Respir Cell Mol Biol. 2006-3
Clin Exp Rheumatol. 2010-11-3
Proc Am Thorac Soc. 2011-11
Int J Chron Obstruct Pulmon Dis. 2025-8-21
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024-12-28
J Clin Invest. 2023-8-15
Cell Commun Signal. 2022-11-1
Eur Respir J. 2015-11
Am J Physiol Lung Cell Mol Physiol. 2013-10-18
World J Cardiol. 2012-12-26
Zotero 插件
