Elevated expression of proteoglycans in proliferating vascular smooth muscle cells
Abstract
Smooth muscle cell (SMC) proliferation and increased production of arterial wall proteoglycans (PG) are implicated in atherogenesis. We investigated the effect of SMC proliferation on the biosynthesis of PG and the ability of the newly synthesized PG to bind low density lipoprotein (LDL). Proliferating and quiescent human aortic SMC were pulsed with [35S]sulfate for 24 h. Secreted and cell-associated PG were then analyzed. When SMC plated at a low density were induced to proliferate, PG synthesis increased significantly in comparison with quiescent cells. 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 in proliferating SMC correlated with a significant increase in the steady-state level of mRNA for perlecan and biglycan, and a modest increase in the versican-specific mRNA. The mRNA for decorin showed a 40% decrease. 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 PG than the corresponding SMC plated at a low density. Although confluent SMC stimulated to proliferate also had increased PG syn...Continue Reading
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