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Gene expression analysis of HUVEC in response to TF-binding
Marianne Grosser1, Viktor Magdolen, Gustavo Baretton
1Institute of Pathology, Technical University of Dresden, D-01307 Dresden, Germany. marianne.grosser@uniklinikum-dresden.de
Thrombosis Research
|December 28, 2010
Summary
Tissue factor (TF) binding to endothelial cells activates gene expression independently of FVIIa. This TF-mediated regulation impacts genes involved in cardiovascular diseases, cancer, and arteriosclerosis.
Area of Science:
- Endothelial cell biology
- Molecular biology
- Gene expression analysis
Background:
- Tissue factor (TF) initiates the extrinsic coagulation pathway and is expressed on intravascular cells.
- Endothelial cells possess a binding site for external TF.
- Understanding TF's role in endothelial cells is crucial for cardiovascular and cancer research.
Purpose of the Study:
- To investigate gene expression changes in human umbilical vein endothelial cells (HUVEC) upon TF binding.
- To identify differentially expressed genes regulated by TF interaction with HUVEC.
- To determine if FVIIa is required for TF-mediated gene regulation in HUVEC.
Main Methods:
- HUVEC were treated with recombinant TF (Innovin) or TF/FVIIa complex.
- TF binding was quantified using ELISA.
- Gene expression profiling was performed using Affymetrix HG-U133 plus 2.0 arrays, with key findings validated by qPCR.
Main Results:
- TF binding to HUVEC resulted in 148 up-regulated and 29 down-regulated genes after 4 hours.
- Gene regulation by TF alone or TF/FVIIa complex showed complete overlap, indicating FVIIa independence.
- TF-mediated regulation affected genes involved in apoptosis, cell adhesion, motility, and angiogenesis.
Conclusions:
- TF interaction with HUVEC occurs via an FVIIa-independent binding site.
- This interaction regulates genes implicated in arteriosclerosis, cancer, and cardiovascular diseases.
- TF binding represents a potential therapeutic target for related pathologies.
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