The effect of tissue factor pathway inhibitor on the expression of monocyte chemotactic protein-3 and IκB-α stimulated by tumour necrosis factor-α in cultured vascular smooth muscle cells

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Abstract

Background: In recent years, the importance of inflammation in restenosis has been recognized gradually. When vascular injury occurs, NF-κB, which controls transcription of many inflammatory genes in restenosis (such as monocyte chemotactic protein-3 [MCP-3]), is activated by IκB degradation, leaving the NF-κB dimer-free to translocate to the nucleus to activate specific target genes. Aims: To investigate the effect of tissue factor pathway inhibitor (TFPI) on MCP-3 expression and IκB-α degradation stimulated by tumour necrosis factor (TNF)-α in vascular smooth muscle cells (VSMCs), thus further elucidating the mechanism of the inhibitory effect of TFPI on restenosis. Methods: Dulbecco's modified Eagle's medium or human recombinant adenoviruses expressing TFPI or bacterial β-galactosidase (LacZ) were used to infect rat aortic VSMCs in vitro. Enzyme-linked immunosorbent assays were used to detect exogenous TFPI expression and reverse transcription-polymerase chain reactions were used to detect MCP-3 expression after TNF-α stimulation in transfected cells. Western blotting and immunofluorescence microscopy were used to examine IκB-α expression. Results: TFPI protein was detected in the TFPI group after gene transfer. The cells were stimulated with TNF-α for 6 hours on the third day after gene transfer. MCP-3 messenger ribonucleic acid expression was lower in the TFPI group than in the LacZ group (P < 0.05) and IκB-α degradation was lower in the TFPI group than in the LacZ group in the cytoplasm (P < 0.05). Conclusion: TFPI inhibited MCP-3 expression induced by TNF-α; this effect may be propagated through the NF-κB pathway. TFPI gene transfer may be a new therapeutic strategy for inhibiting restenosis in clinical situations. © 2012 Elsevier Masson SAS.

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Zhao, Y., Fu, Y., Hu, J., Liu, Y., & Yin, X. (2013). The effect of tissue factor pathway inhibitor on the expression of monocyte chemotactic protein-3 and IκB-α stimulated by tumour necrosis factor-α in cultured vascular smooth muscle cells. Archives of Cardiovascular Diseases, 106(1), 4–11. https://doi.org/10.1016/j.acvd.2012.09.003

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