Modulation of binding to vascular endothelial growth factor and receptor by heparin derived oligosaccharide

We investigated the mechanism of heparin-derived oligosaccharide on the proliferation of vascular smooth muscle cell (VSMC) induced by vascular endothelial growth factor (VEGF). Expression levels of VEGFR 1 and VEGFR 2 were examined by RT-PCR, and the corresponding protein expression levels were detected by Western blotting and immunocytochemistry. Western blotting was taken to identify the expression levels of mechanism proteins. The binding of VEGF and VEGFR 2 was measured by co-IP. Besides, HS competition assay was to detect the ability of HDO to compete with Heparin for VEGF165. HDO showed an inhibitory effect on the expression of VEGFR1/2 proteins and PKC, MAPK, PI3K/Akt pathways. In addition, HDO affected the binding of VEGF-VEGFR, which may be one of the most important mechanisms of HDO suppress the cell proliferation induced by growth factors. Thus HDO showed the ability as a VEGF antagonist.