Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome  

作　　者：Yunchao Su Rudolf Lucas David J.R.Fulton Alexander D.Verin 

机构地区：[1]Department of Pharmacology&Toxicology,Medical College of Georgia,Augusta University,Augusta,GA 30912,USA [2]Division of Pulmonary and Critical Care Medicine,Department of Medicine,Medical College of Georgia,Augusta University,Augusta,GA 30912,USA [3]Vascular Biology Center,Medical College of Georgia,Augusta University,Augusta,GA 30912,USA [4]Research Service,Charlie Norwood Veterans Affairs Medical Center,Augusta,GA 30912,USA

出　　处：《Chinese Medical Journal Pulmonary and Critical Care Medicine》2024年第2期80-87,共8页呼吸与危重症医学（英文）

基　　金：supported,in whole or in part,by NIH grants HL134934 and HL158909 to YS;Augusta University intramural grant IGPCT00023 to YS;by the Department of Veterans Affairs BX005350 to YS.

摘　　要：Endothelial cells(ECs)form a semi-permeable barrier between the interior space of blood vessels and the un-derlying tissues.Pulmonary endothelial barrier integrity is maintained through coordinated cellular processes involving receptors,signaling molecules,junctional complexes,and protein-regulated cytoskeletal reorganiza-tion.In acute lung injury(ALI)or its more severe form acute respiratory distress syndrome(ARDS),the loss of endothelial barrier integrity secondary to endothelial dysfunction caused by severe pulmonary inflamma-tion and/or infection leads to pulmonary edema and hypoxemia.Pro-inflammatory agonists such as histamine,thrombin,bradykinin,interleukin 1𝛽,tumor necrosis factor𝛼,vascular endothelial growth factor,angiopoietin-2,and platelet-activating factor,as well as bacterial toxins and reactive oxygen species,cause dynamic changes in cytoskeletal structure,adherens junction disorganization,and detachment of vascular endothelial cadherin(VE-cadherin)from the actin cytoskeleton,leading to an increase in endothelial permeability.Endothelial interactions with leukocytes,platelets,and coagulation enhance the inflammatory response.Moreover,inflammatory infil-tration and the associated generation of pro-inflammatory cytokines during infection cause EC death,resulting in further compromise of the structural integrity of lung endothelial barrier.Despite the use of potent antibiotics and aggressive intensive care support,the mortality of ALI is still high,because the mechanisms of pulmonary EC barrier disruption are not fully understood.In this review,we summarized recent advances in the studies of endothelial cytoskeletal reorganization,inter-endothelial junctions,endothelial inflammation,EC death,and endothelial repair in ALI and ARDS,intending to shed some light on the potential diagnostic and therapeutic targets in the clinical management of the disease.

关 键 词：LUNG ENDOTHELIUM Pulmonary edema Acute lung injury Acute respiratory distress syndrome 

分 类 号：R563.8[医药卫生—呼吸系统]