title: 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.
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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, China.
authors: Yong
authors: Y
authors: Zhao
authors: Yu
authors: Y
authors: Fu
authors: Jing
authors: J
authors: Hu
authors: Yue
authors: Y
authors: Liu
authors: Xinhua
authors: X
authors: Yin
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D054410:Chemokine CCL7 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C515452:Ccl7 protein, rat; D054410:Chemokine CCL7; D020672:I-kappa B Proteins; D008074:Lipoproteins; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C051928:lipoprotein-associated coagulation inhibitor; D000072000:NF-KappaB Inhibitor alpha