Molecular Mechanisms of Vascular Damage During Lung Injury.
Molecular Mechanisms of Vascular Damage During Lung Injury.
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DOI：
10.1007/978-3-030-68748-9_6
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发表时间：
2021
影响因子：
--
通讯作者：
Adam AP
中科院分区：
文献类型：
--
作者：
Bossardi Ramos R;Adam AP
各种肺部和全身损伤促进炎症反应，导致血管通透性增加，导致急性肺损伤(ALI)，这种情况需要住院和重症监护，或者更严重的急性呼吸窘迫综合征(ARDS)，一种死亡率高的疾病。此外，与新冠肺炎大流行相关的急性呼吸窘迫综合征现在是全球死亡的主要原因。ALI的发病机制是通过对血管内皮细胞和肺泡上皮细胞的损伤来解释的。肺内皮细胞和上皮屏障的破坏是对全身和局部产生促炎细胞因子的反应。评估基因多态与疾病风险之间关系的研究没有得出许多潜在的治疗目标来治疗和逆转肺损伤。这种失败的部分原因可能是ALI/ARDS表型的复杂性，遗传易感性可能被多种环境和行为危险因素所掩盖。在过去的十年中，新的研究发现了控制ALI/ARDS发病的新的表观遗传学机制，包括组蛋白修饰和DNA甲基化。酶抑制剂如DNMTi和HDACi可能提供新的替代策略来预防或逆转肺损伤期间发生的血管损伤。本文将就ALI/ARDS血管损伤的分子机制、可能导致该病易感性的遗传因素、在人类中观察到的表观遗传学变化以及在ALI/ADRS的实验模型中的最新发现作一综述。
A variety of pulmonary and systemic insults promote an inflammatory response causing increased vascular permeability, leading to the development of acute lung injury (ALI), a condition necessitating hospitalization and intensive care, or the more severe acute respiratory distress syndrome (ARDS), a disease with a high mortality rate. Further, COVID-19 pandemic-associated ARDS is now a major cause of mortality worldwide. The pathogenesis of ALI is explained by injury to both the vascular endothelium and the alveolar epithelium. The disruption of the lung endothelial and epithelial barriers occurs in response to both systemic and local production of pro-inflammatory cytokines. Studies that evaluate the association of genetic polymorphisms with disease risk did not yield many potential therapeutic targets to treat and revert lung injury. This failure is probably due in part to the phenotypic complexity of ALI/ARDS and genetic predisposition may be obscured by the multiple environmental and behavioral risk factors. In the last decade, new research has uncovered novel epigenetic mechanisms that control ALI/ARDS pathogenesis, including histone modifications and DNA methylation. Enzyme inhibitors such as DNMTi and HDACi may offer new alternative strategies to prevent or reverse the vascular damage that occurs during lung injury. This review will focus on the latest findings on the molecular mechanisms of vascular damage in ALI/ARDS, the genetic factors that might contribute to the susceptibility for developing this disease, and the epigenetic changes observed in humans, as well as in experimental models of ALI/ADRS.
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