Abstract:

[Abstract]   Objective   To investigate the effects of simvastatin on the expression of lectin-like oxidized low-density
lipoprotein receptor-1(LOX-1) induced by oxidized low-density lipoprotein (ox-LDL) or Glucose in U937      macrophages  ,and explore the role of NF-κB in modulating of LOX-1expression.  Methods   U937macrophages were treated with PMA toinduce differentiation, which were co-cultured with 50mg/L ox-LDL or/and25mmol/L glucose. Pyrrolidine dithiocarbamate(PDTC) and simvastatin (1μmol/L or10μmol/L) were used to treat cells. The expression of LOX-1protein and NF-κB activity were detected by enzyme-linked immunosorbent assay technology. The expression of LOX-1mRNA was measured by RT-PCR.   Results   The expression of LOX-1was up regulated by ox-LDL, glucose and combination of both. The inhibitor of NF-κB PDTC suppressed this up-regulation. Simvastatin suppressed the expression of LOX-1induced by ox-LDL, and showed a significant effect in the higher concentration. There was no significant effect of simvastatin on the expression of LOX-1induced by glucose. The variation of NF-κB activity was similar to that of LOX-1expression.  Conclusion   Simvastatin suppressed the expression of LOX-1induced by ox-LDL, while no significant effect on the expression of LOX-1induced by glucose. The expression and regulation of LOX-1were related with NF-κB pathway.

Key words: lipoproteins, LDL, receptors, LDL, macrophages, NF-kappa B, simvastatin, 氧化型低密度脂蛋白