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Updated: May 8, 2026

Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
Published on: November 22, 2024
p27(Kip1) inhibits tissue factor expression
Alexander Breitenstein1, Alexander Akhmedov, Giovanni G Camici
1Cardiology, University Heart Center, University Hospital Zurich, Switzerland; Cardiovascular Research, Physiology Institute, University of Zurich, Switzerland; Center for Integrative Human Physiology (ZHIP), University of Zurich, Switzerland.
Background:
The cyclin-dependent kinase inhibitor (CDKI) p27(Kip1) regulates cell proliferation and thus inhibits atherosclerosis and vascular remodeling. Expression of tissue factor (TF), the key initator of the coagulation cascade, is associated with atherosclerosis. Yet, it has not been studied whether p27(Kip1) influences the expression of TF.
Methods And Results:
p27(Kip1) overexpression in human aortic endothelial cells was achieved by adenoviral transfection. Cells were rendered quiescent for 24h in 0.5% fetal-calf serum. After stimulation with TNF-α (5 ng/ml), TF protein expression and activity was significantly reduced (n=4; P<0.001) in cells transfected with p27(Kip1). In line with this, p27(Kip1) overexpression reduced cytokine-induced TF mRNA expression (n=4; P<0.01) and TF promotor activity (n=4; P<0.05). In contrast, activation of the MAP kinases p38, ERK and JNK was not affected by p27(Kip1) overexpression.
Conclusion:
This in vitro study suggests that p27(Kip1) inhibits TF expression at the transcriptional level. These data indicate an interaction between p27(Kip1) and TF in important pathological alterations such as atherosclerosis and vascular remodeling.
Insights
The cyclin-dependent kinase inhibitor p27(Kip1) was found to reduce tissue factor (TF) expression in human aortic endothelial cells. This suggests p27(Kip1) may play a role in inhibiting atherosclerosis and vascular remodeling.
Area of Science:
- Vascular Biology
- Cell Cycle Regulation
- Coagulation Cascade
Background:
- p27(Kip1) is a cyclin-dependent kinase inhibitor that regulates cell proliferation and is implicated in inhibiting atherosclerosis and vascular remodeling.
- Tissue factor (TF) initiates the coagulation cascade and its expression is associated with atherosclerosis.
- The relationship between p27(Kip1) and TF expression has not been previously investigated.
Purpose of the Study:
- To investigate the effect of p27(Kip1) on tissue factor (TF) expression in human aortic endothelial cells.
Main Methods:
- Overexpression of p27(Kip1) in human aortic endothelial cells using adenoviral transfection.
- Quiescence of cells followed by stimulation with TNF-α.
- Assessment of TF protein expression, activity, mRNA levels, and promoter activity.
Main Results:
- p27(Kip1) overexpression significantly reduced TF protein expression and activity.
- p27(Kip1) overexpression decreased cytokine-induced TF mRNA expression.
- TF promoter activity was reduced by p27(Kip1) overexpression, while MAP kinase activation remained unaffected.
Conclusions:
- p27(Kip1) inhibits TF expression at the transcriptional level.
- These findings suggest an interaction between p27(Kip1) and TF in pathological processes like atherosclerosis and vascular remodeling.
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