Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation

Vascular development and response to injury are regulated by several cytoki nes and growth factors including the members of the fibroblast growth facto r and vascular endothelial cell growth factor (VEGF) families. Fibrinogen a nd fibrin are also important in these processes and affect many endothelial cell properties. Possible specific interactions between VEGF and fibrinoge n that could play a role in coordinating vascular responses to injury are i nvestigated. Binding studies using the 165 amino acid form of VEGF immobili zed on Sepharose beads and soluble iodine 125 (I-125)-labeled fibrinogen de monstrated saturable and specific binding. Scatchard analysis indicated 2 c lasses of binding sites with dissociation constants (K(d)s) Of 5.9 and 462 nmol/L. The maximum molar binding ratio of VEGF: fibrinogen was 3.8:1, Furt her studies characterized binding to fibrin using I-125-labeled VEGF- and S epharose-immobilized fibrin monomer, These also demonstrated specific and s aturable binding with 2 classes of sites having Kds Of 0.13 and 97 nmol/L a nd a molar binding ratio of 3.6:1, Binding to polymerized fibrin demonstrat ed one binding site with a K-d of 9.3 nmol/L. Binding of VEGF to fibrin(oge n) was independent of FGF-2, indicating that there are distinct binding sit es for each angiogenic peptide. VEGF bound to soluble fibrinogen in medium and to surface immobilized fibrinogen or fibrin retained its capacity to su pport endothelial cell proliferation. VEGF binds specifically and saturably to fibrinogen and fibrin with high affinity, and this may affect the local ization and activity of VEGF at sites of tissue injury. (C) 2000 by The Ame rican Society of Hematology.