VEGF transiently disrupts gap junctional communication in endothelial cells

Area of Science:

• Endothelial cell biology
• Molecular signaling pathways
• Vascular homeostasis

Background:

• Vascular endothelial growth factor (VEGF) is crucial for stimulating angiogenesis via VEGFR-1 and VEGFR-2.
• Endothelial cells rely on cell-cell junctions for network formation and communication.
• Growth factors like EGF and PDGF can disrupt endothelial cell-cell junctions.

Purpose of the Study:

• To investigate early signaling events downstream of VEGF receptors.
• To understand VEGF's effect on endothelial cell-cell communication, specifically gap junctional communication (GJC).
• To identify the molecular mechanisms and signaling pathways involved in VEGF-mediated GJC disruption.

Main Methods:

• Monitoring the transfer of fluorescent tracers between adjacent endothelial cells to assess GJC.
• Utilizing immunofluorescence microscopy to observe changes in cell-cell communication.
• Analyzing the phosphorylation state of connexin 43 (Cx43) following VEGF treatment.

Main Results:

• VEGF maximally blocked GJC within 15 minutes of administration.
• Endothelial cells regained GJC within 1-2 hours post-VEGF treatment.
• VEGF-induced GJC disruption correlated with altered Cx43 phosphorylation and involved VEGFR-2, Src family kinases, and Erk MAP kinases.

Conclusions:

• VEGF rapidly and transiently inhibits GJC in endothelial cells.
• The signaling cascade involves VEGFR-2, Src kinases, and Erk MAP kinases.
• This disruption may serve to limit endothelial permeability at sites of vascular injury.