Heparan sulfate and heparin as a potentiator or a suppressor of growth of normal and transformed vascular endothelial cells.

The effects of glycosaminoglycans (GAGs), especially heparan sulfate, on human and porcine vascular endothelial cell growth in the presence of 10% fetal bovine serum (FBS) or so-called heparin-binding growth factors, acidic FGF (aFGF) or basic FGF (bFGF), were investigated in a series of studies in order to clarify their role in cell proliferation. The promotion of normal cell growth by aFGF was suppressed by heparan sulfate but enhanced by heparin, while growth promotion by bFGF was suppressed by both GAGs. Chondroitin sulfate and hyaluronic acid showed no significant suppression of promotion, even at much higher concentrations. The growth of spontaneously transformed cells was enhanced by heparan sulfate or heparin in the presence of 10% FBS or aFGF, while growth promotion in the presence of bFGF was suppressed by both GAGs. From these results, we concluded that heparan sulfate and heparin are not always functional analogs and that in some cases they exert opposite actions on the modulation of normal endothelial cell growth. The findings that heparan sulfate enhanced the growth of transformed cells but suppressed the growth of normal cells in the presence of 10% FBS or aFGF were consistent with those of our previous studies on human fibroblasts, confirming the occurrence of some common alterations in the signal transduction system or cell surface upon cellular transformation. The role of heparan sulfate in the modulation of endothelial cell proliferation in vivo is also discussed.