Binding and displacement of vascular endothelial growth factor (VEGF) by thrombospondin: effect on human microvascular endothelial cell proliferation and angiogenesis.

摘要: Vascular endothelial growth factor (VEGF) is a specific angiogenic factor, and thrombospondin (TSP), potent inhibitor of angiogenesis. To better understand the role TSP as an anti-angiogenic agent, we have identified its domains that participate in activity examined mechanism inhibitory effect on VEGF(165) induced Exogenously added inhibited angiogenesis (proliferation tube formation human dermal microvascular cells [HDMEC] neovascular outgrowth from arterial rings). Although both are heparin binding proteins, had higher affinity for (125)I-heparin than (K(d1) 4 nM K(d2) 14 TSP; K(d) 91 VEGF(165)). displaced 36% (125)I-VEGF(165) HDMEC this was comparable to 27% reduction upon cleavage cell surface heparan sulfate (HS). About 35% mitogenic attributable region. These results indicate proportion by via competition HS. Further, bound directly saturable, concentration dependent manner, modulated binding. The mAbs domain type 1 3 repeats TSP, also blocked proliferation. We conclude (i) localized (ii) inhibits at least two separate mechanisms, (a) displacement HS (b) direct VEGF(165).