Heparin and endothelial cell growth factor modulate collagen and proteoglycan production in human smooth muscle cells

The effects of heparin and endothelial cell growth factor (ECGF) on extracellular matrix production were examined in human iliac smooth muscle cells. The cells were grown in (a) medium supplemented with heparin (100 micrograms/ml) and ECGF (75 micrograms/ml), (b) medium supplemented with ECGF (75 micrograms/ml) alone, or (c) unsupplemented medium. In the presence of heparin and ECGF, collagen production was inhibited 91-95% as compared to cultures incubated with ECGF alone or without both supplemental factors. In contrast, the production of proteoglycans was elevated 2.5 fold in the presence of heparin and ECGF. Enzymatic digestion of the proteoglycans indicated that both large and small molecular weight chondroitin sulfate proteoglycans were markedly elevated, while dermatan sulfate and heparan sulfate proteoglycans were increased to a lesser extent. The results suggest that the combination of heparin and ECGF elicits potent modulation of extracellular matrix production, with divergent effects on collagen and proteoglycan synthesis.