Abstract:

Objective to investigate the effects of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) on expression of MMP-9  mRNA  in cultured THP-1 monocyte-derived macrophages and the protective effect of simvastatin on it.  MethodsCultured THP-1 monocyte-derived macrophages were incubated with oxLDL(10mg/L, 20mg/L, 50mg/L and 100?mg/L),  pre-incubated with polyinosinic acid and then incubated with 50mg/L ox-LDL, and co-cultured with 100μmol/L simvastatin or 50mg/Lox-LDL. Expressions of LOX-1 and MMP-9mRNA were determined by reverse transcription-polymerase chain reaction(RTPCR). ResultsExpressions of LOX1 and MMP9 mRNA were increased by oxLDL and this was in a concentration-dependent fashion in 1050mg/L（P<0.05）, but were decreased by 100mg/L ox-LDL. The expressions of LOX-1 and MMP-9 were down-regulated in the THP-1 monocyte-derived macrophages by 100μmol/L simvastatin combined with 50mg/L ox-LDL（P<0.05）.  Conclusionox-LDL up-regulates LOX-1 and MMP-9mRNA expressions and LOX-1 may be responsible for expression of MMP-9 in the THP-1 monocyte-derived macrophages, also it can decrease the ox-LDL mediated MMP-9 expression. Simvastatin is able to down-regulate LOX-1 expression in THP-1 monocyte-derived macrophages, corresponding with a decrease of MMP-9 mRNA expression. This in vitro inhibition of LOX-1 might be one new beneficial cardiovascular pieiotroic effect of statins for stabilization of atherosclerotic plaques.

Key words: Lectin-like oxidized low density lipoprotein receptor-1 ； Matrix metalloproteinase-9； Oxidized low density lipoprotein；Monocyte-derived macrophages；  Simvastatin