Effect of low density lipoprotein on glycosaminoglycan secretion by cultured human smooth muscle cells and fibroblasts. Influence of serum concentration and cell proliferation rate.

Glycosaminoglycan (GAG) secretion was studied in cultures of human fibroblasts and arterial smooth muscle cells. Supplementation of culture medium with whole human serum increased the secretion of GAG but this effect disappeared as cell density increased. Lipoprotein-free serum (LFS) supported cell growth but led to a decrease in GAG secretion and in cell cholesterol. Addition of human low density lipoprotein (LDL) to the medium containing 10% LFS produced increases in GAG secretion (200%) and cell cholesterol (300%) and a decrease (60%) in cell population. The effects of LDL were considerably smaller in medium containing 5% LFS; this was related to the lower rate of proliferation in this medium, since there was a close relationship between rate of proliferation and stimulation of GAG secretion by LDL independent of serum concentration. In addition, fetal smooth muscle cells showed a qualitatively different response to LDL in 5% LFS, with a biphasic dose-response of GAG secretion and cell number. It is concluded that: (1) whole human serum stimulates GAG secretion by sparse cell cultures, (2) LFS can support cell growth but not GAG secretion, (3) LDL stimulates GAG secretion but has a cytotoxic effect, (4) the degree of GAG stimulation by LDL is dependent on the proliferative state of cells, (5) at low serum concentrations fibroblasts and fetal smooth muscle cells show differences in response to LDL which are not evident at higher serum concentration.