共 28 条
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.
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页码:466 / 471
页数:6
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