HEPARIN STIMULATES THE PROLIFERATION OF BOVINE AORTIC ENDOTHELIAL-CELLS PROBABLY THROUGH ACTIVATION OF ENDOGENOUS BASIC FIBROBLAST GROWTH-FACTOR

We investigated the effect of heparin on the proliferation of cultured bovine aortic endothelial (BAE) cells. Heparin increased DNA synthesis in BAE cells in a concentration-dependent manner. The DNA synthesis increased by 2 to 2.5-fold with 1 mg/ml of heparin after 48 h incubation without serum and exogenous fibroblast (heparin-binding) growth factors. The stimulating effect of heparin decreased with the diminishing number of monosaccharide units which constitute heparin. By the addition of a neutralizing antibody to basic fibroblast growth factor (bFGF), the stimulating effect of heparin decreased, whereas an antibody to acidic fibroblast growth factor (aFGF) had no effect. The culture medium conditioned by heparin-treated BAE cells stimulated DNA synthesis in Balb/3T3 fibroblasts that proliferate in response to bFGF. The mitogenic activity of the conditioned medium was supressed by the antibody to bFGF. However, heparin did not increase bFGF mRNA level in BAE cells. These results suggest that heparin stimulates the proliferation of BAE cells by the activation of endogenous bFGF, but not by the induction of its synthesis.