Modulation Of Human Vascular Smooth Muscle Cells And Endothelial Cells Growth By Heparan Sulfate Proteoglycan With Relation To Atherosclerosis

It is known that vascular smooth muscle cell(VSMC) proliferation is one of the important atherogenic factor and "injury'' to endothelium is the initiating event of the process. It is also reported that heparan sulfate proteoglycan (HSPG) significantly inhibits the proliferation of VSMC and promotes the growth of endothelial cells,but the mechanisms are far from clear. By using cultured human aortic vascular smooth muscle cells (hASMC) and human umbilical vein endothelial cells (hUVEC) as experimental modals and utilizing ~3H-TdR incorporation, Northern blot analysis, reverse transcription—polymerase chain reaction (RT-PCR), radioimmunoassay (RIA) and colorimetric techniques,the effects of HSPG,extracted from healthy human aorta, on DNA synthesis of hASMC and hUVEC;on the gene expression of platelet-derived growth factor(PDGF),transforming growth factor 3 (TGF-β), basic fibroblaat growth factor(bFGF), angiotensinogen (AngN)and endothelin-1(ET-1);and also on renin-angiotensin system (RAS) were observed in the present study to investigate the possible mechanisms by which HSPG inhibits SMC proliferation and promotes the growth of endothelia(?) cells, which probably provide a theoretical basis for a more effective treatment of atherosclerosis.一 HSPG inhibited both DNA synthesis of hASMC and that induced by exogenous PDGF:As compared to the control group,the ~3H-TdR incorporation was significantly inhibited (10385.2 ±3263.0 VS 25540.5 ± 6421.4 cpm, p<0.01)as quiescent hASMC were cultured with HSPG(15.25 μ g/ml)for 72 h; while it was markedly incrased as with PDGF-AB( 10 μ g/ml), which was inhibited by anti-PDGF antibody (12.5 μ g/ml). HSPG also inhibited DNA synthesis induced by PDGF(7849.0±597.2 VS 13847.1 ± 3175.5 cpm, p<0.01).