VEGF nuclear accumulation correlates with phenotypical changes in endothelial cells.

Area of Science:

• Cell biology
• Molecular biology
• Vascular biology

Background:

• Vascular endothelial growth factor (VEGF) is a key cytokine in vascular biology and pathology.
• Endothelial cells respond to mechanical disruption in wound models.
• VEGF signaling pathways are critical for cellular responses to injury.

Purpose of the Study:

• To investigate the subcellular localization and functional consequences of VEGF internalization in endothelial cells following mechanical wounding.
• To determine the role of nuclear VEGF accumulation in regulating proteins involved in wound healing and hemostasis.

Main Methods:

• Utilized an experimental wound model with cultured endothelial cell monolayers.
• Analyzed VEGF internalization via distinct endocytotic pathways (classical endocytosis vs. rapid nuclear translocation).
• Investigated the effect of nuclear VEGF accumulation on the expression of Factor VIII (FVIII), tissue factor (TF), and tissue plasminogen activator.

Main Results:

• Two distinct endothelial cell subpopulations emerged post-wounding with differential VEGF uptake.
• Cells at wound edges showed rapid VEGF internalization and nuclear translocation, dependent on the KDR binding site.
• Nuclear VEGF accumulation correlated with a rapid, significant increase in FVIII and TF levels, which was blocked by inhibiting nuclear transport.

Conclusions:

• Nuclear accumulation of VEGF in endothelial cells at wound edges plays a role in modulating the expression of key proteins in coagulation and fibrinolysis pathways.
• VEGF's nuclear translocation is a critical mechanism influencing wound healing and hemostatic protein levels.
• Targeting nuclear VEGF transport could offer therapeutic strategies for wound healing and vascular pathologies.