FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis

Abha Sahni, Alok A. Khorana, Raymond B. Baggs, Hu Peng, Charles W. Francis

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

We have shown previously that fibrin(ogen) binds fibroblast growth factor 2 (FGF-2) and potentiates stimulation of endothelial-cell (EC) proliferation. We have now used 2 FGF-2 mutants differing only in the 5 residues constituting the binding site to characterize the importance of this interaction in angiogenesis. The nonbinding (2212) and binding (221*2) mutants stimulated EC proliferation by 2.2 ± 0.4-fold and 2.9 ± 0.3-fold over control, respectively, and both were similar to wild-type (wt) FGF-2 (2.5 ± 0.3-fold). Proliferationwasaugmentedbyfibrinogen to 5.3 ± 1.2-fold and 4.8 ± 0.8-fold with wtFGF-2 and 221*2, whereas no augmentation occurred with 2212 and fibrinogen. Using a placental explant model in a fibrin matrix, wtFGF-2 resulted in 2.6 ± 0.9-fold more growth over control, and 221*2 increased growth 3.3 plus or minus 0.9-fold. Vessel outgrowth with 2212 was minimal and comparable to control. Similarly, fibrinogen potentiated wtFGF-2 or 221*2-mediated angiogenesis in the chicken chorioallantoic membrane model. In a mouse Matrigel implant model, fibrinogen significantly increased angiogenesis with either wtFGF-2 or 221*2, whereas there was no augmentation with 2212. These results demonstrate that binding of FGF-2 to fibrin(ogen) mediated by the 5-residue FGF-2-fibrin(ogen) interactive site is required for augmented angiogenesis.

Original languageEnglish (US)
Pages (from-to)126-131
Number of pages6
JournalBlood
Volume107
Issue number1
DOIs
StatePublished - Jan 1 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Sahni, A., Khorana, A. A., Baggs, R. B., Peng, H., & Francis, C. W. (2006). FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis. Blood, 107(1), 126-131. https://doi.org/10.1182/blood-2005-06-2460