title: FGF-2 but not FGF-1 binds fibrin and supports prolonged endothelial cell growth.
abstract: Endothelial cell viability and growth are dependent on both polypeptide growth factors, and integrin-mediated matrix interactions. We have now examined the ability of fibrin-binding and non-binding growth factors to support long-term endothelial cell growth in the presence or absence of the soluble form. Endothelial cells were cultured on a fibrin surface, with or without FGF-1 or FGF-2, and proliferation was determined by (3)H-thymidine incorporation. Cells cultured on fibrin with no growth factor showed minimal proliferation up to 96 h. In contrast, when FGF-2 was incorporated into fibrin, proliferation was increased 6.5 +/- 0.6-fold, equal to growth on a fibrin surface with FGF-2 continually present in the medium. Thymidine incorporation was similar when cells were cultured on a fibrin surface that had been incubated with FGF-2 and then the growth factor removed (8.6 +/- 0.5-fold). In contrast to results with FGF-2, a surface of fibrin exposed to FGF-1 supported minimal growth, whereas growth was comparable to either FGF-1 or FGF-2 present in the medium. Comparable results were observed when proliferation was quantitated by cell counting at times up to 48 h. Binding studies demonstrated no high-affinity interaction of FGF-1 with fibrinogen or fibrin. We conclude that FGF-2 bound to fibrin supports prolonged endothelial cell growth as well as soluble FGF-2, whereas FGF-1 does not bind to fibrin and can support endothelial cell growth only if continually present in soluble form. Fibrin may serve as a matrix reservoir for FGF-2 to support cell growth at sites of injury or thrombosis.
authors.affiliation: Hematology/Oncology Unit, Department of Medicine, University of Rochester School of Medicine & Dentistry, University Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. abha_sahni@urmc.rochester.edu
authors.forename: A
authors.initials: A
authors.lastname: Sahni
authors.forename: O D
authors.initials: OD
authors.lastname: Altland
authors.forename: C W
authors.initials: CW
authors.lastname: Francis
mesh_terms: D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D005337:Fibrin / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018919:Neovascularization, Physiologic; D011485:Protein Binding; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D005337:Fibrin