Differential effects of gemfibrozil on migration, proliferation and proteoglycan production in human vascular smooth muscle cells
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文摘
The aim of this study was to determine, if gemfibrozil has anti-atherogenic actions on human vascular smooth muscle cells (SMCs) and whether these actions are affected by high glucose concentrations, which mimic the hyperglycemia of diabetes. Proliferation of SMCs treated with gemfibrozil was estimated by cell counting (Coulter Counter) and [3H]thymidine incorporation, migration in a scrape-wound assay, proteoglycan (PG) biosynthesis and glycosaminoglycan (GAG) synthesis on xyloside by [35S]sulfate labeling and sizing by sodium dodecyl sulphide-polyacrylamide gel electrophoresis (SDS-PAGE). Gemfibrozil (100 μmol/l) did not affect migration in low or high glucose media. Gemfibrozil caused concentration-dependent inhibition of proliferation in low glucose media (24 % inhibition at 100 μmol/l, P<0.01) and inhibited the re-initiation of DNA synthesis by 33.3 % (100 μmol/l, P<0.05) in low glucose and 31.4 % (100 μmol/l, P<0.001) in high glucose conditions. In low and high glucose media, gemfibrozil (100 μmol/l) reduced total PG production in the presence of TGF-β1, which was associated with a decrease in the apparent size of PGs. Gemfibrozil and another PPAR-α ligand, WY-14643, significantly inhibited basal and TGF-β1 stimulated GAG synthesis. We conclude that some SMCs properties associated with atherogenesis are favorably affected by gemfibrozil. Hence, direct vascular actions of gemfibrozil observed in this study may contribute to the reduction in cardiovascular disease observed in clinical studies with gemfibrozil.

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