Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice
Fig 10
Postulated model of interactions between VEGF165, VEGFR-2, and CaD.
VEGF165 binds to its co-receptor heparin sulfates (HS) of the endothelial glycocalyx with a specific binding site (left box) which stabilizes the VEGF-VEGF-R binding leading to phosphorylation of VEGFR-2 receptor, intracellular signaling and cell activation (middle box). CaD interacts with the heparin-binding domain of the VEGF165 (right box), thereby displacing HS from its binding site, and decreases VEGF-induced intracellular signaling. CaD also regulates VEGF165 activity by participating in the formation of unstable VEGF-VEGFR-2 complex.