Modulation of proteoglycan synthesis by bovine vascular smooth muscle cells during cellular proliferation and treatment with heparin

Abstract

Proliferating cultures of bovine vascular smooth muscle cells synthesized a variety of proteoglycans corresponding closely to those reported previously for monkey smooth muscle cells. These included a chondroitin sulfate proteoglycan (CSPG) (47%), a dermatan sulfate proteoglycan (DSPG) (22%), and a heparan sulfate proteoglycan (HSPG) (6%) which were secreted into the medium. Heparan sulfate proteoglycan (6%) and a second dermatan sulfate proteoglycan (14%) were also present in the cell layer. Confluent cultures synthesized a similar spectrum of proteoglycans although the medium CSPG and DSPG were of smaller hydrodynamic size. The cell layer HSPG was much reduced relative to DSPG in early proliferating cultures. Previous reports have shown that heparin inhibits vascular smooth muscle cell proliferation. Heparin had two effects on proteoglycan synthesis. In control cultures, 35S-Labeled proteoglycan synthesis doubled during the first 12 h after releasing cells from growth arrest, decreasing during the following 12 h during which time cell division occurred. Treatment with heparin delayed the onset of proliferation by 24 h and this was accompanied by a corresponding delay in the increase in 35S-labeled proteoglycan synthesis associated with the early phase of the cell cycle. Secondly, heparin treatment resulted in an increase in the anionic properties of heparan sulfate proteoglycan synthesized by the cells. This was independent of the proliferative state of the cultures. Pentosan polysulfate, semi-synthetic heparin, and a highly sulfated heparan sulfate modulated both cell proliferation and heparan sulfate proteoglycan synthesis in the same way as heparin.