title: Unfractionated heparin promotes LPS-induced endothelial barrier dysfunction: a preliminary study on the roles of angiopoietin/Tie2 axis.
abstract: BACKGROUND
  Heparins, including unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), are anticoagulants approved as a treatment for severe sepsis, which can also prevent apoptosis and inflammation. The aim of this study was to investigate whether UFH prevents vascular leakage induced by lipopolysaccharide (LPS) and to define the role of angiopoietin (Ang)/Tie2 signaling pathway since LPS is usually used to mimic the initiation of sepsis.
  
  
  METHODS
  Human pulmonary microvascular endothelial cells (HPMECs) were pretreated with UFH (0.1 U/ml-10 U/ml), 15 min prior to stimulation with LPS (10 μg/ml). Those samples not receiving LPS or UFH received an equal volume of Phosphate-buffered saline (PBS). Cells were cultured under various experimental conditions for 2h, 6h or 12h for analysis.
  
  
  RESULTS
  1) Pretreatment with UFH significantly reduced HPMEC permeability compared with LPS-stimulated groups; 2) Pretreatment with UFH decreased the formation of stress fiber and intracellular gaps induced by LPS; 3) UFH significantly up-regulated gene expression of Tie2 and Ang-1 but down-regulated Ang-2 in HPMECs; 4) UFH prevented LPS-induced decrease in the level of ZO-1.
  
  
  CONCLUSIONS
  This study demonstrates that UFH enhances endothelial barrier function and Ang/Tie2 axis probably represents one of the mechanisms by which UFH exerts its protective effect.
authors.affiliation: Department of Intensive Care Unit, the First Affiliated Hospital, China Medical University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yiran
authors.initials: Y
authors.lastname: Mao
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
mesh_terms: D042682:Angiopoietins / Q000378:metabolism*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D042787:Receptor, TIE-2 / Q000378:metabolism*
chemical_list: D042682:Angiopoietins; D006495:Heparin, Low-Molecular-Weight; D008070:Lipopolysaccharides; D006493:Heparin; D042787:Receptor, TIE-2