PMID- 11776326
OWN - NLM
STAT- MEDLINE
DCOM- 20020712
LR  - 20181130
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 86
IP  - 6
DP  - 2001 Dec
TI  - Bemiparin and fluid flow modulate the expression, activity and release of tissue 
      factor pathway inhibitor in human endothelial cells in vitro.
PG  - 1547-54
AB  - We investigated the localisation, gene expression, and activity of tissue factor 
      pathway inhibitor (TFPI) in endothelial cells (EC) grown in static conditions or 
      under shear stress, in the presence of unfractionated heparin (UFH) and two 
      low-molecular-weight heparins (LMWHs). dalteparin and bemiparin (a second 
      generation of LMWHs). All three preparations induced increased release, cellular 
      redistribution, and enhanced activity of TFPI on the cell surface in static EC. 
      In EC grown under shear stress (0.27, 4.1 and 19 dyne/cm2) and incubated with 
      each heparin for 24 h, the release of TFPI was significantly correlated with the 
      level of flow for bemiparin and dalteparin, but not for UFH. For all three levels 
      of flow tested, bemiparin induced the highest secretion and increase of both 
      cellular TFPI and cell surface activity of the inhibitor. The expression of TFPI 
      mRNA, determined by Northern blotting, was specifically modulated by heparins. 
      All three preparations increased the expression of TFPI by 60 to 120% in EC under 
      minimal flow, but only bemiparin enhanced TFPI mRNA in EC under the arterial 
      flow. Immunogold electron microscopy revealed that EC exhibited strong cellular 
      labelling for TFPI when grown under arterial flow in the presence of bemiparin. 
      We conclude that in EC subjected to shear stress in vitro bemiparin is more 
      efficient than UFH or dalteparin in modulating the expression. release and 
      activity of TFPI. We therefore suggest that bemiparin may be superior over the 
      conventional heparins in maintaining the anticoagulant properties of the 
      endothelium.
FAU - Westmuckett, A D
AU  - Westmuckett AD
AD  - Vascular Biology Laboratory, Weston Centre for Experimental Research, Thrombosis 
      Research Institute, London, UK.
FAU - Kakkar, V V
AU  - Kakkar VV
FAU - Hamuro, T
AU  - Hamuro T
FAU - Lupu, F
AU  - Lupu F
FAU - Lupu, C
AU  - Lupu C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anticoagulants)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Lipoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 9005-49-6 (Heparin)
RN  - PUE0TO3XDR (bemiparin)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Anticoagulants/*pharmacology
MH  - Cell Line, Transformed/drug effects
MH  - Cell Membrane/metabolism
MH  - Dalteparin/pharmacology
MH  - Drug Evaluation, Preclinical
MH  - Endothelium, Vascular/*drug effects/enzymology/metabolism
MH  - Fibrinolytic Agents/*pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - *Hemorheology
MH  - Heparin/pharmacology
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Humans
MH  - Immunohistochemistry
MH  - Lipoproteins/biosynthesis/genetics/*metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Secretory Rate/drug effects
MH  - Stress, Mechanical
EDAT- 2002/01/05 10:00
MHDA- 2002/07/13 10:01
CRDT- 2002/01/05 10:00
PHST- 2002/01/05 10:00 [pubmed]
PHST- 2002/07/13 10:01 [medline]
PHST- 2002/01/05 10:00 [entrez]
AID - 01121547 [pii]
PST - ppublish
SO  - Thromb Haemost. 2001 Dec;86(6):1547-54.