Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis

Speaker：葉 承 昀

Commentator：周 楠 華 教授

Time：May 05, 2004; 15:00~16:00

Place：601

Abstract:

      Heparin affin regulatory peptide (HARP) is a heparin-binging molecule involved in the regulation of cell proliferation and differentiation ¹.   VEGF₁₆₅ is a 165 amino acid formof vascular endothelial growth factor, and it can induce migration and mitogenic activity of endothelial cell.  The authors observed that HARP efficiently inhibited VEGF₁₆₅-induced human umbilical vein endothelial cell line (HUVEC) proliferation, tube formation, and infiltration of endothelial cells².  The authors future revealed that HARP could block the interaction between VEGF and VEGF receptor (VEGFR) by competitive affinity-binding aassay.  In addition, the authors made two kinds of dishes that one was labeled VEGFR, and the other was labeled HARP to implement the solid-phase ligand-binding assay.  Beside flt-1 (VEGFR1), the result showed that HARP could block the interaction between VEGF to KDR (VEGFR2) and NP-1, and this function of HARP reduced by heparin.  (VEGFR includes five members, which are VEGFR1, 2, 3, NP-1, and NP-2).  Finally, the authors constructed five mutants, HARP_9-110, HARP_9-59, HARP_60-110, HARP_W20A and HARP_W74A to block the function HARP.  They found that the function of all mutants was lost except the HARP_9-110, indicating that the thrombospondin type-1 repeats domains were involved. These data demonstrate for the first time that the angiogenic factor HARP can also negatively regulates the angiogenic activity of VEGF₁₆₅.

References:

1.       Rauvala, H. An 18-kd heparin-binding protein of developing brain that is distinct from fibroblast growth factors. Embo J 8, 2933-41 (1989).

2.       Heroult, M. et al. Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. Oncogene 23, 1745-53 (2004).