PMID- 22455983
OWN - NLM
STAT- MEDLINE
DCOM- 20121113
LR  - 20120430
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Linking)
VI  - 129
IP  - 5
DP  - 2012 May
TI  - Unfractionated heparin promotes LPS-induced endothelial barrier dysfunction: a 
      preliminary study on the roles of angiopoietin/Tie2 axis.
PG  - e223-8
LID - 10.1016/j.thromres.2012.03.003 [doi]
AB  - INTRODUCTION: 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 mug/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. CONCLUSION: 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.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Li, Xu
AU  - Li X
AD  - Department of Intensive Care Unit, the First Affiliated Hospital, China Medical 
      University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China.
FAU - Zheng, Zhen
AU  - Zheng Z
FAU - Mao, Yiran
AU  - Mao Y
FAU - Ma, Xiaochun
AU  - Ma X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120326
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Angiopoietins)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Lipopolysaccharides)
RN  - 9005-49-6 (Heparin)
RN  - EC 2.7.10.1 (Receptor, TIE-2)
SB  - IM
MH  - Angiopoietins/*metabolism
MH  - Cell Culture Techniques
MH  - Cell Survival/drug effects
MH  - Endothelium, Vascular/cytology/*drug effects/*metabolism
MH  - Heparin/*pharmacology
MH  - Heparin, Low-Molecular-Weight/pharmacology
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Receptor, TIE-2/*metabolism
EDAT- 2012/03/30 06:00
MHDA- 2012/11/14 06:00
CRDT- 2012/03/30 06:00
PHST- 2012/01/07 00:00 [received]
PHST- 2012/02/22 00:00 [revised]
PHST- 2012/03/03 00:00 [accepted]
PHST- 2012/03/30 06:00 [entrez]
PHST- 2012/03/30 06:00 [pubmed]
PHST- 2012/11/14 06:00 [medline]
AID - S0049-3848(12)00129-6 [pii]
AID - 10.1016/j.thromres.2012.03.003 [doi]
PST - ppublish
SO  - Thromb Res. 2012 May;129(5):e223-8. doi: 10.1016/j.thromres.2012.03.003. Epub 
      2012 Mar 26.