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Cardiac glycosides regulate endothelial tissue factor expression in culture
Barbara E Stähli1, Alexander Breitenstein, Alexander Akhmedov
1Cardiovascular Research, Physiology Institute, University of Zürich and Cardiology, University Hospital Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. felix.tanner@access.unizh.ch.
Arteriosclerosis, Thrombosis, and Vascular Biology
|November 22, 2007
Summary
Na(+)/K(+)-ATPase regulates tissue factor (TF) protein expression in endothelial cells by affecting protein translation, not mRNA levels. This finding offers new insights into posttranscriptional regulation of TF.
Area of Science:
- Cardiovascular Biology
- Molecular Cell Biology
- Biochemistry
Background:
- Tissue factor (TF) is crucial in acute coronary syndromes and stent thrombosis.
- Investigating the role of Na(+)/K(+)-ATPase in regulating endothelial TF expression.
Purpose of the Study:
- To determine if Na(+)/K(+)-ATPase influences tissue factor expression in human endothelial cells.
- To elucidate the regulatory mechanisms of TF expression at the posttranscriptional level.
Main Methods:
- Utilized ouabain (a Na(+)/K(+)-ATPase inhibitor) and altered extracellular potassium concentrations.
- Measured TF protein and mRNA expression, TF surface activity, and signaling pathway activation (MAP kinases, Akt, p70S6K, IkappaB-alpha degradation).
Main Results:
- Ouabain significantly inhibited TNF-alpha-induced TF protein expression and surface activity.
- TF mRNA levels were unaffected, but alternatively-spliced TF mRNA was upregulated by ouabain.
- Ouabain did not impact key signaling pathways or TF protein degradation.
Conclusions:
- Na(+)/K(+)-ATPase is essential for endothelial TF protein translation.
- This highlights a novel posttranscriptional regulatory mechanism for TF expression.

