Fffirin(ogen)-bound vascular endothelial growth factor stimulates endothelial cell proliferation

Abha Sahni, Charles W. Francis

Research output: Contribution to journalArticle

Abstract

Fibrin is formed at sites of tissue injury and provides the temporary matrix needed to support the initial endothelial cell responses required for vessel repair. The vascular response to injury is also regulated by peptides of the fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) families. We have, therefore, investigated whether there are specific interactions between VEGF and fibrinogen and fibrin that could play a role in coordinating these actions. Binding studies were performed using the 165 amino acid form of VEGF immobilized on Sepharose beads and soluble p5I-labeled fibrinogen. Binding was saturable and specific with maximum binding occurring at a fibrinogen concentration of 150nM. Scatchard analysis indicated two classes of binding sites with Kds of 5.9 nM and 462 nM. The maximum molar binding ratio of VEGF to fibrinogen was 3.8 to 1. After conversion of Sepharose-immobilized fibrinogen to fibrin by treatment with thrombin, VEGF also demonstrated specific and saturable binding with two classes of binding sites having Kds of 0.13 and 97nM and a molar binding ratio of 3.6 to 1. Fibrin binding was also investigated by clotting a solution of VEGF and fibrinogen by the addition of thrombin, and demonstrated one binding site with a Kd of 9.3 nM. Fibrin(ogen) binding to VEGF was independent of FGF-2, indicating that the binding sites for the two peptides are distinct. VEGF bound to soluble fibrinogen in the medium or to surface-immobilized fibrinogen or fibrin supported endothelial cell proliferation, indicating that it was functionally active. We conclude that VEGF binds specifically and saturably to fibrinogen and fibrin with high affinity and retains activity. This may affect the localization and activity of VEGF at sites of tissue injury and its distribution in the blood.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART II
StatePublished - 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

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