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

doi:10.1067/mva.2003.140

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

Surgery, Vascular Surgery Division

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	650-659
Number of pages	10
Journal	Journal of Vascular Surgery
Volume	37
Issue number	3
DOIs	https://doi.org/10.1067/mva.2003.140
State	Published - Mar 1 2003

Funding

Supported by a grant from the National Institutes of Health (NIH K08 HL04312 01)(S.C.M.) and the Nina Starr Braunwald Resident Research Fellowship (M.R.K.). We thank Karen Fisher, with Genentech, and Karen Schwartz and Richard Lawn, both formerly with Genentech, for providing the rat TF cDNA.

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Surgery

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10.1067/mva.2003.140

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@article{31e3b94706374ab7aafaa42b92adef38,

title = "Regulation of tissue factor expression in smooth muscle cells with nitric oxide",

abstract = "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.",

author = "Kibbe, {Melina R.} and Christopher Johnnides and Susan Gleixner and Imre Kovesdi and Alena Lizonova and Brian Zuckerbraun and Billiar, {Timothy R.} and Edith Tzeng and Muluk, {Satish C.}",

note = "Funding Information: Supported by a grant from the National Institutes of Health (NIH K08 HL04312 01)(S.C.M.) and the Nina Starr Braunwald Resident Research Fellowship (M.R.K.). We thank Karen Fisher, with Genentech, and Karen Schwartz and Richard Lawn, both formerly with Genentech, for providing the rat TF cDNA.",

year = "2003",

month = mar,

day = "1",

doi = "10.1067/mva.2003.140",

language = "English (US)",

volume = "37",

pages = "650--659",

journal = "Journal of Vascular Surgery",

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TY - JOUR

T1 - Regulation of tissue factor expression in smooth muscle cells with nitric oxide

AU - Kibbe, Melina R.

AU - Johnnides, Christopher

AU - Gleixner, Susan

AU - Kovesdi, Imre

AU - Lizonova, Alena

AU - Zuckerbraun, Brian

AU - Billiar, Timothy R.

AU - Tzeng, Edith

AU - Muluk, Satish C.

N1 - Funding Information: Supported by a grant from the National Institutes of Health (NIH K08 HL04312 01)(S.C.M.) and the Nina Starr Braunwald Resident Research Fellowship (M.R.K.). We thank Karen Fisher, with Genentech, and Karen Schwartz and Richard Lawn, both formerly with Genentech, for providing the rat TF cDNA.

PY - 2003/3/1

Y1 - 2003/3/1

N2 - 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.

AB - 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.

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DO - 10.1067/mva.2003.140

M3 - Article

C2 - 12618706

AN - SCOPUS:0037344294

SN - 0741-5214

VL - 37

SP - 650

EP - 659

JO - Journal of Vascular Surgery

JF - Journal of Vascular Surgery

IS - 3

ER -

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

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