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慢性阻塞性肺疾病与心血管系统:血管修复与再生作为治疗靶点

Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target.

作者信息

Karnati Srikanth, Seimetz Michael, Kleefeldt Florian, Sonawane Avinash, Madhusudhan Thati, Bachhuka Akash, Kosanovic Djuro, Weissmann Norbert, Krüger Karsten, Ergün Süleyman

机构信息

Institute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, Würzburg, Germany.

Excellence Cluster Cardio-Pulmonary System (ECCPS), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

出版信息

Front Cardiovasc Med. 2021 Apr 12;8:649512. doi: 10.3389/fcvm.2021.649512. eCollection 2021.

Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and encompasses chronic bronchitis and emphysema. It has been shown that vascular wall remodeling and pulmonary hypertension (PH) can occur not only in patients with COPD but also in smokers with normal lung function, suggesting a causal role for vascular alterations in the development of emphysema. Mechanistically, abnormalities in the vasculature, such as inflammation, endothelial dysfunction, imbalances in cellular apoptosis/proliferation, and increased oxidative/nitrosative stress promote development of PH, cor pulmonale, and most probably pulmonary emphysema. Hypoxemia in the pulmonary chamber modulates the activation of key transcription factors and signaling cascades, which propagates inflammation and infiltration of neutrophils, resulting in vascular remodeling. Endothelial progenitor cells have angiogenesis capabilities, resulting in transdifferentiation of the smooth muscle cells aberrant activation of several cytokines, growth factors, and chemokines. The vascular endothelium influences the balance between vaso-constriction and -dilation in the heart. Targeting key players affecting the vasculature might help in the development of new treatment strategies for both PH and COPD. The present review aims to summarize current knowledge about vascular alterations and production of reactive oxygen species in COPD. The present review emphasizes on the importance of the vasculature for the usually parenchyma-focused view of the pathobiology of COPD.

摘要

慢性阻塞性肺疾病(COPD)是全球发病和死亡的主要原因,包括慢性支气管炎和肺气肿。研究表明,血管壁重塑和肺动脉高压(PH)不仅可发生于COPD患者,也可发生于肺功能正常的吸烟者,提示血管改变在肺气肿发展中起因果作用。从机制上讲,血管系统的异常,如炎症、内皮功能障碍、细胞凋亡/增殖失衡以及氧化/亚硝化应激增加,会促进PH、肺心病的发展,很可能还会促进肺气肿的发展。肺腔中的低氧血症会调节关键转录因子和信号级联反应的激活,从而引发炎症和中性粒细胞浸润,导致血管重塑。内皮祖细胞具有血管生成能力,导致平滑肌细胞转分化以及多种细胞因子、生长因子和趋化因子的异常激活。血管内皮影响心脏血管收缩和舒张之间的平衡。针对影响血管系统的关键因素可能有助于开发针对PH和COPD的新治疗策略。本综述旨在总结目前关于COPD中血管改变和活性氧产生的知识。本综述强调了血管系统对于通常以实质为重点的COPD病理生物学观点的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d427/8072123/277ab6efd435/fcvm-08-649512-g0001.jpg

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