Atorvastatin attenuates atherosclerosis of common carotid artery in apolipoprotein E gene-deficient mice by down-regulating NF-κB

Objective To investigate the effect of atorvastatin on atherosclerosis formation of common carotid artery and its possible mechanism. Methods A total of 36 male apolipoprotein E gene knockout (ApoE-/- ) mice were randomly divided into 3 groups: a control group, a model group, and an atorvastatin group. The mice of the control group were fed with normal diet and received a sham operation, while the mice in the model group and the atorvastatin group were given high fat diet and received a right common carotid artery cannulation. At 5 weeks after procedure, the mice in the model group and the atorvastatin group were intragastric administration of normal saline and atorvastatin (10 mg/kg daily), respectively. At 8 weeks after procedure, the blood from femoral arteries was obtained for biochemical detection, then right common carotid arteries were taken out for histopathological study. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of NF-κB mRNA in the plaques. Western blotting was used to detect phosphorylated NF-κB p65. Results The lipid levels in the model group and the atorvastatin group were significant higher than those in the control group (all P 0.05). The histopathological study showed that the obvious plaque formation and the necrotic core and neovessels in plaques were observed in the model group; obviously thickened intima and more intact endothelial cells in the vessel wall were observed in the atorvastatin group. The plaque burden in the model group and the atorvastatin group was significantly higher than that in the control group (all P<0.001), while the plaque burden in the atorvastatin group was significantly less than that in the model group (P<0.001). Real-time fluorescence quantitative PCR detection showed that the expression levels of NF-κB mRNA in the model group and the atorvastatin group were significantly higher than that in the control group (all P<0.001), and the expression level of NF-κB mRNA in the atorvastatin group was significant lower than that in the model group (P=0.022). Western blotting showed that the expression level of the phosphorylated NF-κB p65 was significantly higher than that of the control group (P<0.001), and the expression level of the phosphorylated NF-κB p65 was significantly lower than that in the model group (P<0.001). Conclusions Atorvastatin may reduce atherosclerosis in the common carotid artery in ApoE-/- ) mice by down-regulating NF-κB. Key words: Atherosclerosis; Carotid Artery, Common; Hydroxymethylglutaryl-CoA Reductase Inhibitors; NF-κB; Inflammation; Disease Models, Animal; Apolipoproteins E; Mice; Atorvastatin