Vascular permeability in the fibrotic lung.
Vascular permeability in the fibrotic lung.
复制标题
纤维化肺中的血管通透性。
DOI：
10.1183/13993003.00100-2019
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
特发性肺纤维化（IPF）被认为是由对慢性或重复性肺损伤的异常组织修复过程引起的。损伤的起源和性质，以及它的细胞和分子靶点，可能是异质的，这使得疾病的准确临床前建模复杂化，并使治疗靶向成为一项挑战。目前正在努力确定纤维形成的中心通路，这可能允许靶向异常修复过程，而不管最初的损伤刺激。内皮通透性异常和血管渗漏在急性肺损伤及其修复中的作用已被研究了很长时间。越来越多的证据表明，这些过程对纤维化肺疾病的发病机制很重要。内皮通透性在非纤维化性肺部疾病中增加，但在细菌性肺炎和急性呼吸窘迫综合征等疾病中以自限性方式消退。然而，在进行性纤维化疾病（如IPF）中，通透性似乎持续存在，并可能预测死亡率。在这篇产生假设的综述中，我们总结了内皮通透性在IPF中的作用的现有数据，并重点关注在肺部炎症和纤维化反应和期间持续内皮高通透性的有害后果。我们认为肺中持续的渗透性和血管渗漏有可能建立和扩大纤维化环境。因此，旨在识别和“堵塞”泄漏的治疗干预措施可能对防止从肺损伤到纤维化的转变有重大益处，这应该是未来研究的领域。
Idiopathic pulmonary fibrosis (IPF) is thought to result from aberrant tissue repair processes in response to chronic or repetitive lung injury. The origin and nature of the injury, as well as its cellular and molecular targets, are likely heterogeneous, which complicates accurate pre-clinical modelling of the disease and makes therapeutic targeting a challenge. Efforts are underway to identify central pathways in fibrogenesis which may allow targeting of aberrant repair processes regardless of the initial injury stimulus. Dysregulated endothelial permeability and vascular leak have long been studied for their role in acute lung injury and repair. Evidence that these processes are of importance to the pathogenesis of fibrotic lung disease is growing. Endothelial permeability is increased in non-fibrosing lung diseases, but it resolves in a self-limited fashion in conditions such as bacterial pneumonia and acute respiratory distress syndrome. In progressive fibrosing diseases such as IPF, permeability appears to persist, however, and may also predict mortality. In this hypothesis-generating review, we summarise available data on the role of endothelial permeability in IPF and focus on the deleterious consequences of sustained endothelial hyperpermeability in response to and during pulmonary inflammation and fibrosis. We propose that persistent permeability and vascular leak in the lung have the potential to establish and amplify the profibrotic environment. Therapeutic interventions aimed at recognising and “plugging” the leak may therefore be of significant benefit for preventing the transition from lung injury to fibrosis and should be areas for future research.
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DOI：
10.1164/ajrccm/140.4.1104
发表时间：
1989-10-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
BROWN, LF;DVORAK, AM;DVORAK, HF
通讯作者：
DVORAK, HF
影响因子：
10.8
作者：
Bates DO
通讯作者：
Bates DO
影响因子：
82.9
作者：
Cao Z;Lis R;Ginsberg M;Chavez D;Shido K;Rabbany SY;Fong GH;Sakmar TP;Rafii S;Ding BS
通讯作者：
Ding BS
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
DOI：
10.1164/rccm.201403-0509pp
发表时间：
2014-10-15
影响因子：
24.7
作者：
Ahluwalia, Neil;Shea, Barry S.;Tager, Andrew M.
通讯作者：
Tager, Andrew M.