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FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis
Abha Sahni1, Alok A Khorana, Raymond B Baggs
1Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. abha_sahni@urmc.rochester.edu
Blood
|September 15, 2005
Summary
Binding of fibroblast growth factor 2 (FGF-2) to fibrinogen is essential for FGF-2 to stimulate angiogenesis. Mutants unable to bind fibrinogen did not promote blood vessel growth, unlike those that could bind.
Area of Science:
- Biochemistry
- Cell Biology
- Vascular Biology
Background:
- Fibrinogen is known to bind fibroblast growth factor 2 (FGF-2).
- This interaction was previously shown to potentiate FGF-2 stimulation of endothelial cell (EC) proliferation.
Purpose of the Study:
- To investigate the role of the FGF-2 binding site on fibrinogen in angiogenesis.
- To characterize the importance of the FGF-2-fibrinogen interaction in stimulating blood vessel formation.
Main Methods:
- Utilized FGF-2 mutants with altered fibrinogen-binding sites.
- Assessed endothelial cell proliferation in vitro.
- Evaluated angiogenesis in placental explant, chicken chorioallantoic membrane, and mouse Matrigel implant models.
Main Results:
- FGF-2 mutants unable to bind fibrinogen (2212) did not show augmented EC proliferation or angiogenesis in the presence of fibrinogen.
- FGF-2 mutants that could bind fibrinogen (221*2) and wild-type FGF-2 showed potentiated EC proliferation and angiogenesis with fibrinogen.
- Fibrinogen significantly enhanced FGF-2-mediated angiogenesis in all tested in vivo models only when FGF-2 could bind to fibrinogen.
Conclusions:
- The specific 5-residue interaction site between FGF-2 and fibrinogen is critical for FGF-2-potentiated angiogenesis.
- Binding of FGF-2 to fibrinogen is a prerequisite for augmented blood vessel formation stimulated by FGF-2.