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CD40 ligation induces tissue factor expression in human vascular smooth muscle cells
U Schönbeck1, F Mach, G K Sukhova
1Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
The American Journal of Pathology
|January 7, 2000
Summary
The CD40/CD40L signaling pathway promotes tissue factor (TF) expression in vascular smooth muscle cells (SMC). This interaction may increase plaque thrombogenicity during atherosclerosis and arterial injury.
Area of Science:
- Cardiovascular Biology
- Immunology
- Thrombosis Research
Background:
- Tissue factor (TF) initiates blood coagulation and is implicated in atherosclerotic events.
- TF expression in atherosclerotic lesions is known, but its regulation in vascular smooth muscle cells (SMC) is unclear.
Purpose of the Study:
- To investigate the role of CD40/CD40L signaling in regulating TF expression and procoagulant activity in vascular SMC.
- To determine if CD40 and TF colocalize on SMC within human atherosclerotic lesions.
Main Methods:
- Immunohistochemistry to assess TF and CD40 colocalization in human atherosclerotic lesions.
- Flow cytometry (FACS) and ELISA to measure TF expression on cultured vascular SMC stimulated with CD40 ligand (CD40L).
- Assays to evaluate the functional activity of CD40L-induced TF and tissue factor pathway inhibitors.
Main Results:
- TF colocalizes with CD40 on SMC within human atherosclerotic lesions.
- CD40L stimulation induced transient and dose-dependent TF expression on vascular SMC cell surfaces.
- CD40L-induced TF was functional, activating coagulation without affecting tissue factor pathway inhibitor levels.
Conclusions:
- The CD40/CD40L pathway augments the procoagulant activity of human vascular SMC by increasing TF expression.
- CD40/CD40L signaling may contribute to plaque thrombogenicity in atherogenesis and arterial injury due to TF upregulation.