title: Simvastatin Attenuates Acute Lung Injury via Regulating CDC42-PAK4 and Endothelial Microparticles.
abstract: Simvastatin has lung vascular-protective effects via augmentation of endothelial barrier function. Accordingly, on the basis of our previous study, we hypothesized that endothelial cell (EC) protection by simvastatin is dependent on the stabilization on cytoskeletons.
  
  
  
  Sixty C57BL/6 mice were divided into two experimental groups: lipopolysaccharide (LPS) group (L group) and LPS+simvastatin treated group (L+S group). All mice in these two groups received an intraperitoneal injection of LPS (10 mg/kg/d). Simvastatin was administered intraperitoneally immediately after the LPS injection in animals of the L+S group at a dose of 20 mg/kg/day. Lung injury degree and the protective effects of simvastatin against LPS-induced lung injury were assessed at the time-points of 24, 48, and 72 h postinjection. Serum alanine transaminase (ALT), serum creatinine (Scr) were identified to assess the hepatic and renal side-effects of simvastatin.
  
  
  
  LPS inhibited the cytoskeletal regulating proteins of Cdc42 and PAK4, and was accompanied by an increased circulating endothelial microparticles (EMPs) level. The adherent junction (AJ) protein of VE-cadherin was also decreased by LPS, and was accompanied by a thickening alveolar wall, increased lung W/D values, and high albumin concentration in bronchoalveolar lavage. Protective effects of simvastatin against LPS-induced lung injury were illustrated by regulating and stabilizing cytoskeletons, as well as intercellular AJs. The values of ALT and Scr were all lower than the common upper limits according to assay kits.
  
  
  
  An increased serous EMP level associated with Cdc42-PAK4 can be deemed as a useful pulmonary injury marker in LPS-treated mice, and our results might be more relevant in guiding the clinical treatment of ALI by intervening Cdc42-PAK4 or EMPs.
authors: *Emergency Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China †Emergency Department, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China ‡Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Yang
authors: Y
authors: Yu
authors: Lihong
authors: L
authors: Jing
authors: Xiangyu
authors: X
authors: Zhang
authors: Chengjin
authors: C
authors: Gao
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D018893:Bronchoalveolar Lavage; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019821:Simvastatin / Q000627:therapeutic use*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D019821:Simvastatin; C492065:Pak4 protein, mouse; D054462:p21-Activated Kinases; D020764:cdc42 GTP-Binding Protein