Abstract
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.
Keywords: Lung injury; Vascular damage; Epithelial barrier; Endothelial activation; Epigenetics; Histone acetylation, DNA methylation; Inflammation.
【저자키워드】 Inflammation, Lung injury, epigenetics, endothelial activation, Vascular damage, Epithelial barrier, Histone acetylation, DNA methylation, 【초록키워드】 COVID-19, Respiratory distress syndrome, ARDS, Risk factors, Cytokines, Pathogenesis, Mortality, intensive care, acute respiratory distress syndrome, Hospitalization, susceptibility, Genetic, vascular permeability, Lung injury, molecular mechanism, epigenetics, acute lung injury, DNA, humans, Research, pro-inflammatory cytokines, genetic polymorphisms, DNA methylation, disease, epithelial, change, Epigenetic, mechanism, experimental model, association, ADRS, acute respiratory distress, histone, Inflammatory response, Genetic polymorphism, Injury, Vascular damage, Genetic predisposition, Disruption, genetic factors, focus, respiratory distress, Enzyme inhibitors, behavioral risk factors, Vascular endothelium, Factor, molecular mechanisms, syndrome, treat, phenotypic, high mortality rate, Modification, disease risk, potential therapeutic target, experimental models, offer, lung endothelial, Enzyme inhibitor, alveolar epithelium, Prevent, increased vascular permeability, evaluate, contribute, explained, occur, variety, promote, systemic and local, 【제목키워드】 damage,