Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1

Parul Houston, Marion Dickson, Valerie Ludbrook, Brian White, Jean-Luc Schwachtgen, John H. McVey, Nigel Mackman, Jason Reese, Daniel Gorman, Callum Campbell, Martin Braddock

Research output: Contribution to journalArticle

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Abstract

AB Hemodynamic forces such as fluid shear stress have been shown to modulate the activity of an expanding family of genes involved in vessel wall homeostasis and the pathogenesis of vascular disease. We have investigated the effect of shear stress on tissue factor (TF) gene expression in human endothelial cells (ECs) and in a rat arterial model of occlusion. As measured by reverse transcriptase polymerase chain reaction, exposure of ECs to 1.5 N/m2 shear stress resulted in a time-dependent induction of endogenous TF transcripts of over 5-fold. Transient transfection of TF promoter mutants into cultured ECs suggests the involvement of the transcription factor Egr-1 in mediating the response of the TF promoter to shear stress. To address the importance of flow induction of Egr-1 in vivo, we have established a flow-restricted rat arterial model and determined the level of expressed Egr-1 and TF at the site of restricted flow using immunohistochemistry. We report an increase in the level of Egr-1 and TF protein in ECs expressed at the site of restricted flow. Elevated expression of Egr-1 and TF is restricted to a highly localized area, as evidenced by the fact that no significant increase in level can be detected at arterial sites distal to the site of occlusion. These findings suggest a direct role for Egr-1 in flow-mediated induction of TF and further substantiate the importance of shear stress as a modulator of vascular endothelial gene function in vivo. (Arterioscler Thromb Vasc Biol. 1999;19:281-289.)

LanguageEnglish
Pages281-289
JournalArteriosclerosis Thrombosis, and Vascular Biology
Volume19
Issue number2
Publication statusPublished - 1 Feb 1999

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Thromboplastin
Endothelial Cells
In Vitro Techniques
Reverse Transcriptase Polymerase Chain Reaction
Vascular Diseases
Genes
Transfection
Blood Vessels
Cultured Cells
Homeostasis
Transcription Factors
Hemodynamics
Immunohistochemistry
Gene Expression

Cite this

Houston, P., Dickson, M., Ludbrook, V., White, B., Schwachtgen, J-L., McVey, J. H., ... Braddock, M. (1999). Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1. Arteriosclerosis Thrombosis, and Vascular Biology, 19(2), 281-289.
Houston, Parul ; Dickson, Marion ; Ludbrook, Valerie ; White, Brian ; Schwachtgen, Jean-Luc ; McVey, John H. ; Mackman, Nigel ; Reese, Jason ; Gorman, Daniel ; Campbell, Callum ; Braddock, Martin. / Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1. In: Arteriosclerosis Thrombosis, and Vascular Biology. 1999 ; Vol. 19, No. 2. pp. 281-289.
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Houston, P, Dickson, M, Ludbrook, V, White, B, Schwachtgen, J-L, McVey, JH, Mackman, N, Reese, J, Gorman, D, Campbell, C & Braddock, M 1999, 'Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1' Arteriosclerosis Thrombosis, and Vascular Biology, vol. 19, no. 2, pp. 281-289.

Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1. / Houston, Parul; Dickson, Marion; Ludbrook, Valerie; White, Brian; Schwachtgen, Jean-Luc; McVey, John H.; Mackman, Nigel; Reese, Jason; Gorman, Daniel; Campbell, Callum; Braddock, Martin.

In: Arteriosclerosis Thrombosis, and Vascular Biology, Vol. 19, No. 2, 01.02.1999, p. 281-289.

Research output: Contribution to journalArticle

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T1 - Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1

AU - Houston, Parul

AU - Dickson, Marion

AU - Ludbrook, Valerie

AU - White, Brian

AU - Schwachtgen, Jean-Luc

AU - McVey, John H.

AU - Mackman, Nigel

AU - Reese, Jason

AU - Gorman, Daniel

AU - Campbell, Callum

AU - Braddock, Martin

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N2 - AB Hemodynamic forces such as fluid shear stress have been shown to modulate the activity of an expanding family of genes involved in vessel wall homeostasis and the pathogenesis of vascular disease. We have investigated the effect of shear stress on tissue factor (TF) gene expression in human endothelial cells (ECs) and in a rat arterial model of occlusion. As measured by reverse transcriptase polymerase chain reaction, exposure of ECs to 1.5 N/m2 shear stress resulted in a time-dependent induction of endogenous TF transcripts of over 5-fold. Transient transfection of TF promoter mutants into cultured ECs suggests the involvement of the transcription factor Egr-1 in mediating the response of the TF promoter to shear stress. To address the importance of flow induction of Egr-1 in vivo, we have established a flow-restricted rat arterial model and determined the level of expressed Egr-1 and TF at the site of restricted flow using immunohistochemistry. We report an increase in the level of Egr-1 and TF protein in ECs expressed at the site of restricted flow. Elevated expression of Egr-1 and TF is restricted to a highly localized area, as evidenced by the fact that no significant increase in level can be detected at arterial sites distal to the site of occlusion. These findings suggest a direct role for Egr-1 in flow-mediated induction of TF and further substantiate the importance of shear stress as a modulator of vascular endothelial gene function in vivo. (Arterioscler Thromb Vasc Biol. 1999;19:281-289.)

AB - AB Hemodynamic forces such as fluid shear stress have been shown to modulate the activity of an expanding family of genes involved in vessel wall homeostasis and the pathogenesis of vascular disease. We have investigated the effect of shear stress on tissue factor (TF) gene expression in human endothelial cells (ECs) and in a rat arterial model of occlusion. As measured by reverse transcriptase polymerase chain reaction, exposure of ECs to 1.5 N/m2 shear stress resulted in a time-dependent induction of endogenous TF transcripts of over 5-fold. Transient transfection of TF promoter mutants into cultured ECs suggests the involvement of the transcription factor Egr-1 in mediating the response of the TF promoter to shear stress. To address the importance of flow induction of Egr-1 in vivo, we have established a flow-restricted rat arterial model and determined the level of expressed Egr-1 and TF at the site of restricted flow using immunohistochemistry. We report an increase in the level of Egr-1 and TF protein in ECs expressed at the site of restricted flow. Elevated expression of Egr-1 and TF is restricted to a highly localized area, as evidenced by the fact that no significant increase in level can be detected at arterial sites distal to the site of occlusion. These findings suggest a direct role for Egr-1 in flow-mediated induction of TF and further substantiate the importance of shear stress as a modulator of vascular endothelial gene function in vivo. (Arterioscler Thromb Vasc Biol. 1999;19:281-289.)

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Houston P, Dickson M, Ludbrook V, White B, Schwachtgen J-L, McVey JH et al. Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1. Arteriosclerosis Thrombosis, and Vascular Biology. 1999 Feb 1;19(2):281-289.