VEGF-E Attenuates Injury After Ischemic Stroke by Promoting Reparative Revascularization

Area of Science:

• Neuroscience
• Vascular Biology
• Regenerative Medicine

Background:

• Stroke-induced angiogenesis is crucial for recovery but can be destabilized by vascular endothelial growth factor (VEGF)-A.
• VEGF-A therapy carries risks of vascular complications.
• VEGF-E, a VEGF-A homolog, promotes stable vascularization and wound healing.

Purpose of the Study:

• To investigate VEGF-E as a potential therapeutic for reparative revascularization after ischemic stroke.
• To compare the efficacy and safety of VEGF-E versus VEGF-A in a mouse stroke model.

Main Methods:

• Experimental stroke was induced in C57BL6/J mice.
• VEGF-E or VEGF-A was delivered intranasally during the subacute phase.
• Neurological recovery, vascular density, permeability, and brain perfusion were assessed.
• Cell-based assays examined endothelial cell-pericyte interactions and signaling pathways (PDGF-D, ERK, MAPK).

Main Results:

• VEGF-E improved neurological recovery and increased vascular density without compromising permeability, outperforming VEGF-A.
• VEGF-E restored normal brain perfusion, while VEGF-A caused hyperperfusion.
• VEGF-E enhanced endothelial cell-pericyte interactions and reduced microvascular stalls.
• VEGF-E increased PDGF-D expression and activated ERK/MAPK signaling in brain endothelial cells.
• VEGF-E-stimulated endothelial cells promoted pericyte migration.

Conclusions:

• VEGF-E promotes stable and functional revascularization after ischemic stroke.
• VEGF-E offers a safer and more effective alternative to VEGF-A for stroke therapy.
• VEGF-E's therapeutic potential for ischemic stroke warrants further investigation.