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

被引:28
作者
Demetz, G. [1 ,2 ]
Seitz, I. [1 ,2 ]
Stein, A. [1 ,2 ]
Steppich, B. [1 ,2 ]
Groha, P. [1 ,2 ]
Brandl, R. [3 ]
Schoemig, A. [1 ,2 ]
Ott, I. [1 ,2 ]
机构
[1] Tech Univ Munich, Deutsch Herzzentrum, D-80636 Munich, Germany
[2] Tech Univ Munich, Med Klin 1, D-80636 Munich, Germany
[3] Klinikum Schwabing, Klin Gefasschirurg, D-80804 Munich, Germany
关键词
Tissue Factor; FVIIa; PAR-2; Smooth muscle cells; Inflammation; ENDOTHELIAL-CELLS; UP-REGULATION; ACTIVATION; INTERLEUKIN-8; IL-8; MONOCYTES; CANCER; MACROPHAGES; RECEPTOR-2; LEUKOCYTES;
D O I
10.1016/j.atherosclerosis.2010.07.017
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:466 / 471
页数:6
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