BINDING OF PLATELET-DERIVED GROWTH-FACTOR AND LOW-DENSITY LIPOPROTEINS TO GLYCOSAMINOGLYCAN SPECIES PRODUCED BY HUMAN ARTERIAL SMOOTH-MUSCLE CELLS

The platelet-derived growth factor (PDGF) binds via a defined amino ac id sequence to heparin (Fager et al., 1992, In Vitro Cell. Dev. Biol., 28A:176-180) and the protein moiety of low density lipoproteins (LDL; apo B-100) via a similar sequence to chondroitin sulfate (Camejo et a l., 1988, Arteriosclerosis Thromb., 8:368-377). In this study, synthet ic oligopeptides were used to explore the capacity of smooth muscle ce ll-derived glycosaminoglycans to bind to the critical sequences of PDG F and apo B-100. In vitro, proliferating human arterial smooth muscle cells synthesized twice as much proteoglycans as did quiescent cells. The dominating glycosaminoglycan side chains were chondroitin and hepa ran sulfates in secreted and cell-associated proteoglycans, respective ly. The chondroitin sulfate-rich proteoglycans had a higher molecular size and were to a larger extent secreted into the culture medium than the heparan and dermatan sulfate-rich proteoglycans. Heparan, dermata n, and chondroitin sulfates bound to the PDGF-derived oligopeptide wit h affinities similar to those of heparin. However, while heparan and d ermatan sulfates both inhibited DNA synthesis in human arterial smooth muscle cells, chondroitin sulfate had no such inhibitory effect. Like the PDGF-derived oligopeptide, the apo B-100-derived oligopeptide bou nd to these glycosaminoglycans. At the same time, both oligopeptides d isplaced bound LDL from chondroitin sulfate in vitro and released the block on DNA synthesis in smooth muscle cells that heparin induced in culture. Thus, chondroitin, dermatan, and heparan sulfates produced by arterial smooth muscle cells may bind LDL and PDGF competitively in a therogenesis but only heparan and dermatan sulfates inhibit cellular D NA synthesis. LDL and PDGF deposition may occur by binding to similar binding sites on glycosaminoglycans derived from smooth muscle cells w ithin atherosclerotic lesions. (C) 1995 Wiley-Liss, Inc.