Effect of atorvastatin on advanced glycation end products induced monocyte chemoattractant protein-1 expression in cultured human endothelial cells / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of atorvastatin on advanced glycation end products (AGE) induced monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVECs) and whether this effect could be linked to peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor-κB (NF-κB).</p><p><b>METHODS</b>Grouping (1) Blank control group; (2) BSA group; (3) AGE group cells were incubated with different concentrations of AGE (10(-4), 10(-3), 10(-2) and 10(-1) g/L) for 24 hours; (4) AGE + Atorvastatin group cells were incubated with different concentrations of atorvastatin (0.1, 1, 10 µmol/L) for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (5) PPAR-γ agonist (15 d-PGJ2) group cells were incubated with 15 d-PGJ2 (10 µmol/L) for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (6) PPAR-γ inhibitor (GW9662) group cells were incubated with GW9662 (5000 nmol/L) for 1 hour, then incubated with atorvastatin (1 µmol/L) and AGE (10(-1) g/L) for 24 hours. Collagenase was used to isolate the endothelial cell from human umbilical vein; RT-PCR was performed to examine the mRNA expression of MCP-1 and PPAR-γ; Western blot was performed to detect NF-κB p65 protein.</p><p><b>RESULTS</b>(1) The expression of MCP-1 mRNA was increased in proportion with increasing concentrations of AGEs which could be blocked by atorvastatin in a dose-dependent manner. (2) AGE (10(-1) g/L) significantly downregulated the expression of PPAR-γ mRNA (0.22 ± 0.08 vs. 0.69 ± 0.09, P < 0.01) while upregulated the expression of phospho-NF-κB p65 protein (0.78 ± 0.06 vs. 0.31 ± 0.01, P < 0.01) and nonphospho-NF-κB p65 protein (1.61 ± 0.16 vs. 0.59 ± 0.14, P < 0.01) compared with the control group which could be significantly attenuated by atorvastatin. (3) PPAR-γ agonist decreased the expression of phospho-NF-κB p65 protein (0.21 ± 0.01 vs. 0.78 ± 0.06, P < 0.01), nonphospho-NF-κB p65 protein (0.67 ± 0.14 vs. 1.61 ± 0.16, P < 0.01) and MCP-1 mRNA (0.17 ± 0.02 vs. 0.93 ± 0.12, P < 0.01) compared with AGE (10(-1) g/L) group. (4) PPAR-γ inhibitor antagonized the effect of atorvastatin on the expression of phospho-NF-κB p65 protein, nonphospho-NF-κB p65 protein and MCP-1 mRNA stimulated by AGE in HUVECs (P < 0.01).</p><p><b>CONCLUSION</b>The anti-inflammatory properties of atorvastatin in AGE stimulated HUVECs may partly be attributed to the effect on upregulation of PPAR-γ and downregulation of NF-κB signaling pathway.</p>