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Upregulation of TRAF-3 by shear stress blocks CD40-mediated endothelial activation
1Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany.
The Journal of Clinical Investigation
|November 21, 2001
Summary
Shear stress, a blood flow force, prevents artery inflammation by increasing TNF receptor-associated factor-3 (TRAF-3). This mechanism inhibits CD40-induced endothelial cell activation, protecting blood vessels.
Area of Science:
- Cardiovascular Biology
- Inflammation Research
- Endothelial Cell Biology
Background:
- Atherosclerosis is an inflammatory arterial disease initiated by endothelial cell activation.
- CD40 receptor stimulation is implicated in atherosclerosis development.
- Endothelial shear stress is a key atheroprotective stimulus.
Purpose of the Study:
- To investigate the protective mechanisms of endothelial shear stress against CD40 ligand-induced activation.
- To identify molecular mediators involved in shear stress-mediated atheroprotection.
Main Methods:
- Cultured endothelial cells were subjected to shear stress.
- Expression levels of TNF receptor-associated factor-3 (TRAF-3) were analyzed.
- Overexpression of TRAF-3 was performed to assess its functional impact.
- Analysis of proinflammatory cytokine and tissue factor expression, and AP-1 DNA-binding activity.
Main Results:
- Shear stress specifically upregulates TRAF-3 expression in endothelial cells.
- TRAF-3 expression is elevated in areas of high shear stress overlying human atherosclerotic plaques.
- Overexpression of TRAF-3 inhibits CD40-induced endothelial activation, including proinflammatory cytokine and tissue factor expression.
- TRAF-3 overexpression blocks AP-1 DNA-binding activity.
Conclusions:
- Upregulation of TRAF-3 is a novel mechanism by which shear stress inhibits CD40-induced endothelial activation.
- TRAF-3 plays a critical role in preserving endothelial integrity under inflammatory conditions.
- Targeting TRAF-3 may offer a therapeutic strategy for atherosclerosis.
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