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Tissue factor activity is increased in human endothelial cells cultured under elevated static pressure
M D Silverman1, C R Waters, G T Hayman
1Laboratory of Cell Biology, Department of Medicine, University of Wisconsin Medical School, Milwaukee Clinical Campus at Sinai-Samaritan Medical Center, Milwaukee, Wisconsin 53201, USA.
The American Journal of Physiology
|August 13, 1999
Summary
Elevated blood pressure increases tissue factor (TF) activity in human endothelial cells, independent of TF gene expression. This suggests pressure affects cell membranes, potentially impacting hemostasis and atherosclerosis risk.
Area of Science:
- Cardiovascular Biology
- Hemostasis Research
- Cellular Physiology
Background:
- Elevated blood pressure is a risk factor for atherosclerosis and causes vascular remodeling.
- Tissue factor (TF) is crucial in blood coagulation and thrombosis.
- Endothelial cells (EC) play a key role in regulating vascular tone and hemostasis.
Purpose of the Study:
- To investigate if elevated blood pressure modulates basal and cytokine-induced tissue factor (TF) expression in human endothelial cells (EC).
- To determine the effect of increased pressure on TF activity, mRNA, and cell surface expression.
- To explore the underlying mechanisms, including plasma membrane alterations.
Main Methods:
- Human aortic EC (HAEC) and vena cava EC (HVCEC) were cultured under atmospheric and elevated (170 mmHg) pressure.
- TF activity was measured using a chromogenic enzymatic assay.
- TF mRNA levels and cell surface antigen expression were assessed via quantitative RT-PCR and ELISA.
- Plasma membrane permeability was evaluated using merocyanine 540 uptake.
Main Results:
- Elevated pressure significantly increased basal TF activity in both HAEC and HVCEC.
- Pressurization further enhanced TNF-alpha-induced TF activity in both cell types.
- TF mRNA and cell surface antigen expression were not altered by pressure, but membrane permeability increased.
- These findings suggest pressure modulates TF activity via plasma membrane changes, not gene expression.
Conclusions:
- Elevated static pressure enhances both basal and cytokine-stimulated TF activity in human EC.
- Pressure-induced modulation of TF activity appears to be independent of TF gene expression.
- Changes in EC plasma membrane organization and/or permeability may underlie the observed effects on hemostatic potential.