Shear stress regulates inflammatory and thrombogenic gene transcripts in cultured human endothelial progenitor cells

Trine Lund; Stig E. Hermansen; Thomas V. Andreasen; Jan Ole Olsen; Bjarne Østerud; Truls  Myrmel; Kirsti Ytrehus

doi:10.1160/TH09-12-0854

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(03): 582-591
DOI: 10.1160/TH09-12-0854

Endothelium and Vascular Development

Schattauer GmbH

Shear stress regulates inflammatory and thrombogenic gene transcripts in cultured human endothelial progenitor cells

Authors

Trine Lund

¹Cardiovascular Research Group, Department of Medical Biology, University of Tromsø, Tromsø, Norway
Stig E. Hermansen

²Department of Clinical Medicine, University of Tromsø, Tromsø, Norway

³Department of Cardiothoracic and Vascular Surgery, University Hospital of North Norway, Tromsø, Norway
Thomas V. Andreasen

¹Cardiovascular Research Group, Department of Medical Biology, University of Tromsø, Tromsø, Norway
Jan Ole Olsen

⁴Department of Medical Biology, University of Tromsø, Tromsø, Norway
Bjarne Østerud

⁴Department of Medical Biology, University of Tromsø, Tromsø, Norway
Truls Myrmel

²Department of Clinical Medicine, University of Tromsø, Tromsø, Norway

³Department of Cardiothoracic and Vascular Surgery, University Hospital of North Norway, Tromsø, Norway
Kirsti Ytrehus

¹Cardiovascular Research Group, Department of Medical Biology, University of Tromsø, Tromsø, Norway

Abstract

Summary

Shear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with unfavourable properties. The aim of the present study was therefore to assess whether shear stress may influence the inflammatory and thrombotic phenotype of in vitro expanded EPCs. In late outgrowth EPCs, 6 hours of shear stress (6.0 dynes/ cm²) significantly reduced the mRNA levels of IL-8, COX2, and tissue factor (TF) compared to static controls. This was associated with a reduced TF activity. In contrast, mRNA expression of NOS3 was significantly increased following 6 and 24 hours of shear stress. In accordance with this, NOS3 protein expression was increased following 24 hours of shear stress. Overall stimulation with the proinflammatory mediator, TNFα, for the final 2 hours increased the mRNA expression of IL-6, IL-8, MCP-1, ICAM1, and TF. However exposure to 6 hours of shear stress significantly suppressed the inductory potential of TNFα to increase the mRNA levels of IL-6, IL-8, COX2, and TF. Additionally, TNFα increased TF activity approximately 10 times, an effect that was also significantly reduced by exposure to 6 and 24 hours of shear stress. The effect of shear on the gene levels of TF and NOS3 were not blocked by the NOS inhibitor L-NAME. These observations suggest that EPCs are capable of functionally responding to shear stress.

Keywords

Late outgrowth endothelial progenitor cells - shear stress - inflammation - tissue factor

Full Text

References

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