Stimulation of smooth muscle cell glycosaminoglycan synthesis by cultured endothelial cells is dependent on endothelial cell density.

Smooth muscle cells (SMC) cultured in the presence of endothelial cells (EC), or in EC-conditioned medium, show increased synthesis of glycosaminoglycans (GAG). We have found that both the amount and type of GAG produced by the SMC are dependent on the density of the EC. EC (porcine) at a low density (0.1-0.5 X 10(6) cells/25 cm2), or their conditioned media, where the most active per cell in stimulating GAG. All GAG were stimulated but the increase was due mostly to hyaluronic acid (HA). At intermediate densities (1.0 X 10(6)/25 cm2) stimulation was markedly reduced, but still present, and both HA and sulphated GAG were similarly increased. At high densities (1.5-3 X 10(6)/25 cm2) where EC were confluent there was very little stimulation of HA but continued stimulation of sulphated GAG synthesis. The shift in stimulation from HA to sulphated GAG with increasing density was most clearly demonstrated by the decrease in the HA to the chondroitin sulphate ratio. These findings provide support for the general concept that SMC metabolism may be affected by changes in the state of the endothelium.