title: Continuous blood purification ameliorates RhoA-mediated endothelial permeability in severe acute pancreatitis patients with lung injury.
abstract: BACKGROUND
  In the early phase of severe acute pancreatitis (SAP), serious pulmonary complications which are directly correlated with mortality are very common. Endothelial injury has been shown to play a key role in the pathogenesis of ALI/ARDS. Continuous blood purification (CBP) has been widely used in treating patients with multiple organ dysfunction syndrome (MODS) including ARDS. However, the impact of CBP on endothelial function has been little studied.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were exposed to serum samples or replacement fluid taken from patients at specific time points during CBP, or pretreated with Y-27632 followed by treatment with serum, then, changes in cytoskeletal configuration, endothelial monolayer permeability, and RhoA activation were studied.
  
  
  RESULTS
  Endothelial permeability, RhoA activity, and stress fiber reorganization increased in HUVECs treated with serum from patients before CBP initiation, and lessened in HUVECs treated with serum from patients after CBP initiation. Endothelial hyperpermeability and stress fiber reorganization reduced in HUVECs pretreated with Rho-kinase inhibitor, Y-27632, and in a dose-dependent fashion. Endothelial permeability and RhoA activity increased in HUVECs treated with waste replacement fluid collected 2 h after CBP initiation.
  
  
  CONCLUSIONS
  After CBP treatment, endothelial hyperpermeability induced by serum from SAP patients with lung injury was reduced. The inhibition of RhoA-mediated F-actin remodeling might be the mechanism.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing - PR China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Du
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Gan
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Li
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Wen
authors.forename: Xi-Chao
authors.initials: XC
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000208:Acute Disease; D055371:Acute Lung Injury / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000628:therapy*; D000328:Adult; D000577:Amides / Q000494:pharmacology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002681:China; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D006440:Hemofiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000628:therapy*; D010539:Permeability; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012720:Severity of Illness Index; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D000577:Amides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C066737:RHOA protein, human; C108830:Y 27632; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein