Bemiparin and Fluid Flow Modulate the Expression, Activity and Release of Tissue Factor Pathway Inhibitor in Human Endothelial Cells In Vitro

Andrew D. Westmuckett; Vijay V. Kakkar; Tsutomu Hamuro; Florea Lupu; Cristina Lupu

doi:10.1055/s-0037-1616761

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(06): 1547-1554
DOI: 10.1055/s-0037-1616761

Review Article

Schattauer GmbH

Bemiparin and Fluid Flow Modulate the Expression, Activity and Release of Tissue Factor Pathway Inhibitor in Human Endothelial Cells In Vitro

Andrew D. Westmuckett

¹Vascular Biology Laboratory, Weston Centre for Experimental Research, Thrombosis Research Institute, London, UK

²Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, USA

,

Vijay V. Kakkar

¹Vascular Biology Laboratory, Weston Centre for Experimental Research, Thrombosis Research Institute, London, UK

,

Tsutomu Hamuro

³Chemo-Sero-Therapeutic Research Institute ‘Kaketsuken’, Kumamoto, Japan

,

Florea Lupu

¹Vascular Biology Laboratory, Weston Centre for Experimental Research, Thrombosis Research Institute, London, UK

²Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, USA

,

Cristina Lupu

¹Vascular Biology Laboratory, Weston Centre for Experimental Research, Thrombosis Research Institute, London, UK

²Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, USA

› Author Affiliations

Abstract

Summary

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.

Keywords

TFPI - human endothelial cells - heparin - shear stress

Full Text

References

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