Atorvastatin suppresses Toll-like receptor 4 expression and NF-κB activation in rabbit atherosclerotic plaques.
BACKGROUND
Toll-like receptor 4 (TLR4) plays an essential role in the pathogenesis and progression of atherosclerosis, which overexpresses in atherosclerotic lesions and mediates the production of inflammatory factors. The aim of this study was to investigate the effects of atorvastatin on TLR4 protein and mRNA expression and its downstream factor NF-κB activation in rabbit atherosclerotic plaques.


METHODS
Rabbits continuously fed with high-fat diet for 24 weeks were randomly divided into two groups, the drug-treated group orally administrated with atorvastatin (2 mg/kg/day) three weeks after high-fat diet feeding and the model group with no treatment. The expression of TLR4 protein and mRNA, the level of activated NF-κB (p65) were respectively detected by western blotting, quantitative RT-PCR, and ELISA.


RESULTS
The results showed that atorvastatin treatment reduced the expression of TLR4 protein and mRNA by 24.1% (p < 0.05) and 46.9% (p < 0.01), respectively, and also inhibited NF-κB activation by 76.0% (p < 0.001) in the atherosclerotic plaques.


CONCLUSIONS
Thus, it was suggested that atorvastatin could exert an anti-atherosclerotic activity besides inhibiting cholesterol biosynthesis.
Department of Gastroenterology Medicine, Shanghai Eighth People's Hospital, Shanghai, China. quanzheq@hotmail.com  
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D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D000069059:Atorvastatin; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000493:pharmacokinetics*; D016328:NF-kappa B / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000378:metabolism*; D011758:Pyrroles / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D006538:Heptanoic Acids; D016328:NF-kappa B; D011758:Pyrroles; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D000069059:Atorvastatin