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

摘要

Background: In recent years, the importance of inflammation in restenosis has been recognized gradually. When vascular injury occurs, NF-??B, which controls transcription of many inflammatory genes in restenosis (such as monocyte chemotactic protein-3 [MCP-3]), is activated by I??B degradation, leaving the NF-??B 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 I??B-?? degradation stimulated by tumour necrosis factor (TNF)-?? 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 ??-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-?? stimulation in transfected cells. Western blotting and immunofluorescence microscopy were used to examine I??B-?? expression. Results: TFPI protein was detected in the TFPI group after gene transfer. The cells were stimulated with TNF-?? 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 I??B-?? 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-??; this effect may be propagated through the NF-??B pathway. TFPI gene transfer may be a new therapeutic strategy for inhibiting restenosis in clinical situations. ? 2012 Elsevier Masson SAS.