Multiple mechanisms for exogenous heparin modulation of vascular endothelial growth factor activity

摘要: Heparin and heparin-like molecules are known to modulate the cellular responses vascular endothelial growth factor-A (VEGF-A). In this study, we investigated likely mechanisms for heparin's influence on biological activity of VEGF-A. Previous studies have shown that exogenous effects VEGF-A many varied, in part due endogenous cell-surface heparan sulfates. To circumvent problem, used mutant cells lacking We showed VEGF-induced dependent presence sulfates, heparin significantly augments VEGF's especially when sulfates absent. Exogenous was also found play a cross-bridging role between VEGF-A(165) putative heparin-binding sites within its cognate receptor, VEGFR2 they were examined isolation. The appears be more molecular weight than specific structure. This confirmed by surface plasmon resonance binding using sugar chips immobilized with defined oligosaccharide structures, which binds relatively broad range sulfated glycosaminoglycan structures. Finally, far-UV circular dichroism spectra can conformation secondary structure protein.