ELEVATED EXPRESSION OF PROTEOGLYCANS IN PROLIFERATING VASCULAR SMOOTH-MUSCLE CELLS

Smooth muscle cell (SMC) proliferation and increased production of art erial wall proteoglycans CPG) are implicated in atherogenesis. We inve stigated the effect of SMC proliferation on the biosynthesis of PG and the ability of the newly synthesized PG to bind low density lipoprote in (LDL). Proliferating and quiescent human aortic SMC were pulsed wit h [S-35]sulfate for 24 h. Secreted and cell-associated PG were then an alyzed. When SMC plated at a low density were induced to proliferate, PC synthesis increased significantly in comparison with quiescent cell s. This was the net result of a 2.7-fold increase in secreted PG and a 1.3-fold increase in cell-associated PG. The increased PG synthesis i n proliferating SMC correlated with a significant increase in the stea dy-state level of mRNA for perlecan and biglycan, and a modest increas e in the versican-specific mRNA. The mRNA for decorin showed a 40% dec rease. The increased PG secretion in proliferating cultures was due to increases in heparan sulfate PG, dermatan sulfate PG, and chondroitin sulfate PG secretion. Quiescent SMC at confluency produced 50% less P G than the corresponding SMC plated at a low density. Although conflue nt SMC stimulated to proliferate also had increased PG synthesis, this was 50% less than the PG synthesis by proliferating SMC that were ini tially plated at a low density. The PG synthesized by proliferating an d quiescent SMC did not differ in charge density and molecular size. S ecreted PG from both quiescent and proliferating cultures contained su bfractions that bound LDL with high affinity. However, compared with q uiescent cultures, the proliferating cultures produced more of a PG su bfraction that exhibited very high affinity to LDL (31.6% in quiescent cultures versus 40.8% in proliferating cultures). These results indic ate that PG metabolism is altered significantly in proliferating human SMC which might have implications in the pathophysiology of atheroscl erosis. (C) 1997 Elsevier Science Ireland Ltd.