Regulation of tissue factor expression in smooth muscle cells with nitric oxide

Melina R. Kibbe, Christopher Johnnides, Susan Gleixner, Imre Kovesdi, Alena Lizonova, Brian Zuckerbraun, Timothy R. Billiar, Edith Tzeng, Satish C. Muluk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Objective: This study was undertaken to determine the effect of nitric oxide (NO) on tissue factor (TF) expression in vascular smooth muscle cells. Study design: Rat aortic smooth muscle cells (RASMCs) were exposed to NO delivered exogenously with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) or produced endogenously after infection with an adenoviral vector carrying human inducible NO synthase (AdiNOS). Functional TF activity was assessed with chromogenic TF assay. TF antigen was determined with immunohistochemistry. Northern blot analysis was used to determine steady-state TF messenger RNA (mRNA). Electrophoretic mobility gel shift assay was performed to determine the nuclear binding activity of nuclear factor κ-B (NFκB). NFκB activity was inhibited by either prior transduction of RASMCs with mutant IκB or treatment with pyrrolidine dithiocarbamate. Results: RASMCs exposed to SNAP or infected with AdiNOS exhibited increased functional TF activity and antigen. Regardless of the source of NO, a time-dependent and concentration-dependent increase in TF activity was observed. Steady-state TF mRNA levels were also increased by NO delivered via either method. NFκB nuclear binding activity was also increased by NO. Inhibition of NFκB activity by either pyrrolidine dithiocarbamate treatment or mutant IκB transduction abrogated NO-induced enhancement of TF mRNA and functional activity. Conclusion: In RASMC, NO exposure results in upregulation of TF functional activity, antigen, and mRNA. This effect appears to be mediated by an NFκB-dependent pathway.

Original languageEnglish
Pages (from-to)650-659
Number of pages10
JournalJournal of Vascular Surgery
Issue number3
StatePublished - 1 Mar 2003
Externally publishedYes


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