PLATELET-DERIVED GROWTH-FACTOR STIMULATES THE SECRETION OF HYALURONIC-ACID BY PROLIFERATING HUMAN VASCULAR SMOOTH-MUSCLE CELLS

Total glycans from the cell layer and the culture medium of human vasc ular smooth muscle cells (VSMC) that had been cultivated in the presen ce of platelet-derived growth factor (PDGF) were isolated and purified by gel filtration after Pronase and DNase digestion and alkali-borohy dride treatment, Measurements of the content of neutral hexoses and ur onic acids revealed that PDGF stimulates total glycan synthesis by pro liferating VSMC in a linear fashion from 24 h to 72 h of incubation, I n contrast, total glycan synthesis by human fibroblasts, epithelial ce lls, or endothelial cells was not affected by PDGF, indicating cell-ty pe specificity, Chemical, biochemical, and enzymological characterizat ion of the total glycans synthesized by VSMC showed that PDGF stimulat es the secretion of a 340-kDa glycan molecule in a time-dependent mann er from 24 h to 72 h, This molecule is highly acidic, shares a common structure with hyaluronic acid, and exhibits a potent antiproliferativ e activity on VSMC, These results suggest that VSMC in response to PDG F are capable of controlling their own growth and migration by the syn thesis of a specific form of hyaluronic acid with antiproliferative po tency, which may be involved in the regulation of the local inflammato ry responses associated with atherosclerosis.