title: Increased Circulating Endothelial Microparticles Associated with PAK4 Play a Key Role in Ventilation-Induced Lung Injury Process.
abstract: Inappropriate mechanical ventilation (MV) can result in ventilator-induced lung injury (VILI). Probing mechanisms of VILI and searching for effective methods are current areas of research focus on VILI. The present study aimed to probe into mechanisms of endothelial microparticles (EMPs) in VILI and the protective effects of Tetramethylpyrazine (TMP) against VILI. In this study, C57BL/6 and TLR4KO mouse MV models were used to explore the function of EMPs associated with p21 activated kinases-4 (PAK-4) in VILI. Both the C57BL/6 and TLR4 KO groups were subdivided into a mechanical ventilation (MV) group, a TMP + MV group, and a control group. After four hours of high tidal volume (20 ml/kg) MV, the degree of lung injury and the protective effects of TMP were assessed. VILI inhibited the cytoskeleton-regulating protein of PAK4 and was accompanied by an increased circulating EMP level. The intercellular junction protein ofβ-catenin was also decreased accompanied by a thickening alveolar wall, increased lung W/D values, and neutrophil infiltration. TMP alleviated VILI via decreasing circulating EMPs, stabilizing intercellular junctions, and alleviating neutrophil infiltration.
authors.affiliation: Emergency Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Pan
authors.affiliation: Emergency Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Fei
authors.affiliation: Emergency Department, The Affiliated Hospital of Qingdao University, Shandong 266100, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Emergency Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Chengjin
authors.identifier: 0000-0002-6867-8024
authors.initials: C
authors.lastname: Gao
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002448:Cell Adhesion; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism; D055370:Lung Injury / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D011719:Pyrazines / Q000737:chemistry; D012121:Respiration, Artificial / Q000009:adverse effects*; D012129:Respiratory Function Tests; D013990:Tidal Volume; D051197:Toll-Like Receptor 4 / Q000235:genetics; D055397:Ventilator-Induced Lung Injury / Q000097:blood*; D051176:beta Catenin / Q000378:metabolism; D054462:p21-Activated Kinases / Q000097:blood*
chemical_list: D011719:Pyrazines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051176:beta Catenin; C492065:Pak4 protein, mouse; D054462:p21-Activated Kinases; C017953:tetramethylpyrazine