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Basic science: Cardiovascular disease basic research
e0010 Atorvastatin inhibits oxidised low density lipoprotein induced differentiation of RAW2647 murine macropahges into dendritic like cells
  1. Liu Hua Hu
  1. Renji Hospital Medical College of Shanghai Jiaotong University

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells and have an important role in the pathogenesis of atherosclerosis. It has been confirmed that the optimal oxLDL dose (10 ug/ml) can induce approximatelly 74% RAW264.7 cells differentiate into dendritic-like cells in our previous work. In this study, we examined whether atorvastatin could inhibit the differentiation of mature macrophages into DCs induced by oxLDL, since statins are lipid-lowering drugs. After 24 h treatment with atorvastatin (20 umol/ml), almost all the RAW264.7 cells induced by oxLDL simultaneously remained in cell size and macrophages morphology compared with those induced by oxLDL alone. Flow cytometric analysis detected reduced dendritic cell surface markers (CD40, CD86, MHC Class II and CD1d, table 1). Moreover, atorvastatin-treated RAW264.7 cells induced by oxLDL shown functional changes including increased phagocytic ability (table 2) in a time-dependent manner and reduced TNF-a as well as IL-12 p70 (table 3) productin. On the whole, these data suggest dendritic-like cells origined from macrophages induced by oxLDL treatment can be inhibited by atorvastatin and this may contribute to the effect of statins on preventing the formation of atherosclerotic plaques.

Table 1. dendritic cell surface markers expression (%) in 24 h RAW OxLDL OxLDL+atorvastatin CD40 6.09%±0.48% 51.68%±1.33% * 40.09%±1.59% * CD86 5.00%±0.62% 55.04%±1.27% * 24.29%±1.30% * CD1d MHC Class II 3.64%±0.41% 5.09%±0.13% 33.79%±2.47% * 17.10%±1.42% * 33.40%±11.54% * 22.87%±6.665 * compared with RAW, p<0.05 Table 2. FITC DEXTRAN uptake (%) Atorvastatin OxLDL OxLDL+atorvastatin 6 h 15.89%±0.25% 18.62%±0.45% * 18.12%±0.76% 12 h 23.96%±1.83% 36.50%±1.27% * 29.39%±0.50% * 24 h 25.07%±0.76% 26.55%±0.37 30.10%±0.21 *% FITC DEXTRAN uptake by RAW is 17.35%±0.28%; * compared with Atorvastatin, p<0.05 Table 3. TNF-a (ng/ml) and IL-12 p70 (pg/ml) productin in 24 h DMEM+10%FCS OxLDL OxLDL+atorvastatin TNF-a 0.142±0.04 4.010±0.34 * 1.656±0.252 * IL-12 p70 34.06±5.65 172.89±33.90 * 72.03±5.62 * compared with DMEM+10% FCS, p<0.05.

Table 1

dendritic cell surface markers expression (%) in 24 hs

Table 2

FITC DEXTRAN uptake (%)

Table 3

TNF-a (ng/ml) and IL-12 p70 (pg/ml) productin in 24 hs

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