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http://purl.uniprot.org/citations/20708733http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20708733http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Within atherosclerotic lesions Tissue Factor (TF)-Factor VIIa (FVIIa) not only contributes to thrombotic events but also alters vascular remodeling through enhancement of migration. Moreover, the TF-FVIIa-FXa complex activates protease-activated receptors (PAR). TF/FVIIa/PAR-2 signaling has also been shown to promote proliferation and metastasis of tumor cells. Since coagulation factors promote inflammation which plays a major role during atherosclerosis as well as tumor metastasis this study sought to investigate the effects of FVIIa on the inflammatory response in vascular cells.

Methods/results

FVIIa induces interleukin-8 (IL-8) and IL-6 in primary smooth muscle cells (SMC), which was correlated to the expression of TF and PAR-2 as shown by immunoassay and qRT-PCR. The effect was dose-dependent and required TF, the proteolytic activity of FVIIa and PAR-2. Secondary effects of downstream coagulation factors were excluded. No proinflammatory FVIIa effect was observed in endothelial cells (EC) and mononuclear cells (MNC), expressing either TF or PAR-2. In atherosclerotic lesions mRNA expression of PAR-1, PAR-2 and IL-8 was elevated compared to healthy vessels indicating a role for PAR-1 and PAR-2 signaling in atherosclerosis.

Conclusion

In addition to the procoagulant and promigratory role of the TF-FVIIa complex we identify a proinflammatory role of FVIIa in human SMC dependent on expression of TF and PAR-2 that provides yet another link between coagulation and inflammation."xsd:string
http://purl.uniprot.org/citations/20708733http://purl.org/dc/terms/identifier"doi:10.1016/j.atherosclerosis.2010.07.017"xsd:string
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/author"Seitz I."xsd:string
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/author"Schomig A."xsd:string
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/author"Stein A."xsd:string
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/author"Brandl R."xsd:string
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http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/author"Steppich B."xsd:string
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http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/author"Groha P."xsd:string
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/name"Atherosclerosis"xsd:string
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/pages"466-471"xsd:string
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/title"Tissue Factor-Factor VIIa complex induces cytokine expression in coronary artery smooth muscle cells."xsd:string
http://purl.uniprot.org/citations/20708733http://purl.uniprot.org/core/volume"212"xsd:string
http://purl.uniprot.org/citations/20708733http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20708733
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