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Updated: May 26, 2026
Generation of Human CD40-activated B cells
Published on: October 17, 2009
CD40 ligand inhibits endothelial cell migration by increasing production of endothelial reactive oxygen species
Carmen Urbich1, Elisabeth Dernbach, Alexandra Aicher
1Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany.
Insights
CD40 ligand (CD40L) inhibits endothelial cell migration by increasing reactive oxygen species, hindering plaque stabilization and potentially increasing acute coronary event risk. This impacts endothelial regeneration after plaque erosion.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Biology
Background:
- The CD40/CD40 ligand (CD40L) system plays a role in atherosclerosis.
- Activated T lymphocytes and platelets expressing CD40L contribute to plaque instability and thrombus formation, leading to acute coronary syndromes.
- Endothelial cell (EC) migration is crucial for plaque stabilization through reendothelialization.
Purpose of the Study:
- To investigate the role of CD40L in endothelial cell migration.
- To understand the mechanisms by which CD40L affects EC migration and its implications for atherogenesis.
Main Methods:
- Utilized a "scratched wound assay" to assess EC migration.
- Investigated the effects of recombinant CD40L, activated T lymphocytes, and platelets on EC migration and tube formation in vitro.
- Analyzed the role of nitric oxide (NO) and reactive oxygen species (ROS) in CD40L-mediated inhibition of EC migration.
Main Results:
- Recombinant CD40L, activated T lymphocytes, and platelets inhibited vascular endothelial growth factor (VEGF)-induced EC migration and tube formation.
- CD40L stimulation induced ROS production and reduced endothelial NO bioavailability, thereby inhibiting EC migration.
- The inhibitory effect of CD40L on EC migration was dependent on ROS and could be reversed by antioxidants like vitamin C or N-acetylcysteine.
Conclusions:
- CD40 receptor activation inhibits EC migration primarily by increasing reactive oxygen species.
- CD40L-mediated blockade of EC migration may impair endothelial regeneration following plaque erosion.
- This impaired regeneration contributes to the elevated risk of acute coronary events in individuals with high circulating CD40L levels.
Background:
The CD40/CD40 ligand system is involved in atherogenesis. Activated T lymphocytes and platelets, which express high amounts of CD40 ligand (CD40L) on their surface, contribute significantly to plaque instability with ensuing thrombus formation, leading to acute coronary syndromes. Because reendothelialization may play a pivotal role for plaque stabilization, we investigated a potential role of CD40L on endothelial cell (EC) migration.
Methods And Results:
Stimulation of ECs with recombinant CD40L prevented vascular endothelial growth factor (VEGF)-induced EC migration, as determined by a "scratched wound assay." In addition, activated T lymphocytes and platelets significantly inhibited VEGF-induced EC migration and tube formation in vitro. Because the activation of endothelial nitric oxide (NO) synthase and the release of NO are required for EC migration and angiogenesis, we analyzed the effect of NO. Coincubation with the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) did not reverse the inhibitory effect of CD40L on VEGF-induced EC migration and tube formation. In addition, EC migration induced by SNAP was completely inhibited by CD40L. CD40L, however, induced the production of reactive oxygen species and reduced endothelial NO bioavailability. This reactive oxygen species-dependent effect of CD40L stimulation was reversed with vitamin C or N-acetylcysteine.
Conclusions:
The activation of the CD40 receptor inhibits EC migration by increasing reactive oxygen species. The blockade of EC migration by CD40L may critically affect endothelial regeneration after plaque erosion and thereby may contribute to the increased risk for development of acute coronary events in patients with high circulating levels of CD40L.
