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

Abha Sahni, Charles W. Francis

Research output: Contribution to journalArticle

293 Citations (Scopus)

Abstract

Vascular development and response to injury are regulated by several cytokines and growth factors including the members of the fibroblast growth factor and vascular endothelial cell growth factor (VEGF) families. Fibrinogen and fibrin are also important in these processes and affect many endothelial cell properties. Possible specific interactions between VEGF and fibrinogen that could play a role in coordinating vascular responses to injury are investigated. Binding studies using the 165 amino acid form of VEGF immobilized on Sepharose beads and soluble iodine 125 (125I)-labeled fibrinogen demonstrated saturable and specific binding. Scatchard analysis indicated 2 classes 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. Further studies characterized binding to fibrin using 125I-labeled VEGF- and Sepharose-immobilized fibrin monomer. These also demonstrated specific and saturable binding with 2 classes of sites having K(d)S of 0.13 and 97 nmol/L and a molar binding ratio of 3.6:1. Binding to polymerized fibrin demonstrated one binding site with a K(d) of 9.3 nmol/L. Binding of VEGF to fibrin(ogen) was independent of FGF-2, indicating that there are distinct binding sites for each angiogenic peptide. VEGF bound to soluble fibrinogen in medium and to surface immobilized fibrinogen or fibrin retained its capacity to support endothelial cell proliferation. VEGF binds specifically and saturably to fibrinogen and fibrin with high affinity, and this may affect the localization and activity of VEGF at sites of tissue injury. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)3772-3778
Number of pages7
JournalBlood
Volume96
Issue number12
StatePublished - Dec 1 2000
Externally publishedYes

Fingerprint

Endothelial cells
Cell proliferation
Fibrin
Fibrinogen
Vascular Endothelial Growth Factor A
Cell growth
Endothelial Cells
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Binding Sites
Sepharose
Blood Vessels
Wounds and Injuries
Angiogenic Proteins
Fibroblast Growth Factors
Fibroblast Growth Factor 2
Iodine
Cytokines
Amino Acids
Tissue

ASJC Scopus subject areas

  • Hematology

Cite this

Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation. / Sahni, Abha; Francis, Charles W.

In: Blood, Vol. 96, No. 12, 01.12.2000, p. 3772-3778.

Research output: Contribution to journalArticle

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