Tissue Factor-Factor VIIa complex induces cytokine expression in coronary artery smooth muscle cells

G. Demetz, I. Seitz, A. Stein, B. Steppich, P. Groha, R. Brandl, A. Schömig, I. Ott

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)466-471
Number of pages6
JournalAtherosclerosis
Volume212
Issue number2
DOIs
StatePublished - Oct 2010

Keywords

  • FVIIa
  • Inflammation
  • PAR-2
  • Smooth muscle cells
  • Tissue Factor

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