Potentiation of endothelial cell proliferation by fibrin(ogen)-bound fibroblast growth factor-2

Endothelial cell growth is stimulated by fibroblast growth factor-2 (FGF-2) , and both adhesion and proliferation are modulated by interactions with fi brinogen and fibrin. Previous evidence indicates that FGF-2 binds specifica lly and with high affinity to fibrinogen and fibrin, suggesting that their effects on endothelial cells may be coordinated. In this study, we have, th erefore, investigated the ability of FGF-2 bound to fibrinogen and fibrin t o stimulate proliferation of endothelial cells. Human umbilical vein endoth elial cells were cultured in the presence of FGF-2 with or without fibrinog en, and proliferation was assessed by microscopic examination of cultures, incorporation of [H-3]thymidine and by cell counting. Cells cultured in the presence of both FGF-2 and fibrinogen proliferated more rapidly than those with FGF-2 alone and exhibited a decreased population doubling time. At co ncentrations of FGF-2 up to 150 ng/ml, there was greater endothelial cell p roliferation in the presence of fibrinogen than in its absence with the mos t pronounced effect below 1 ng/ml. The maximum effect of fibrinogen was obs erved at a molar ratio of fibrinogen to FGF-2 of 2:1, corresponding to the maximum molar binding ratio. Endothelial cells proliferated when plated on fibrin or surface-immobilized fibrinogen with FGF-2, indicating that FGF-2 bound to surface-associated fibrin(ogen) retained activity. We conclude tha t fibrinogen- or fibrin-bound FGF-2 is able to support endothelial cell pro liferation and that fibrinogen potentiates the proliferative capacity of FG F-2.