Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Factor Xa is a serine protease integral to the clotting cascade that has also been implicated in immune and inflammatory responses. Effector cell protease receptor-1 (EPR-1), a receptor for factor Xa, was recently shown to be present on vascular endothelial and smooth muscle cells and to mediate calcium mobilization, cytokine and growth factor production and cell proliferation in vitro. We now show that factor Xa exhibits vasoactive properties in vivo. Systemic administration of factor Xa to anesthetized rats caused a hypotensive response. In the perfused rat mesentery, vasodilation in response to Xa was attenuated by inhibition of nitric oxide (NO) production. Experiments with cultured human endothelial cells revealed that NO release requires binding of the catalytically active factor Xa to EPR-1. NO was also found to mediate, at least in part, the factor Xa-induced increase in IL-6 gene expression as well as IL-6 protein secretion. These results establish a novel role for factor Xa as a link between hemostasis and vascular tone and implicate the NO/cGMP signaling pathway as a mediator of the biologic actions of factor Xa in the vessel wall.

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Presentation Number SApapapetropoulos0882
Keywords: nitric oxide, endothelium, factor Xa, cGMP