title: [Atorvastatin inhibits macrophage-derived foam cell formation by suppressing the activation of PPARγ and NF-κB pathway].
abstract: OBJECTIVE
  To evaluate whether atorvastatin inhibits oxidized low-density lipoproteins (Ox-LDL)-stimulated foam cell formation from THP-1 macrophages by regulating the activation of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor-κB (NF-κB). Methods THP-1 macrophages were pretreated with 10, 20, or 40 µmol/L atorvastatin for 2 h, and after washing with PBS twice, the cells were incubated with 60 µg/ml of Ox-LDL for 48 h. The quantity of intracellular lipid of the cells was detected with Oil red O staining and enzymatic fluorometric method. The expression of the scavenger receptors of CD36 and SRA were analyzed with Western blotting. We also examined the effect of atorvastatin on adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and the activation of PPARγ and p-iκB, and further assessed the capacity of the macrophages to bind to Dil-oxLDL.
  
  
  RESULTS
  Atorvastatin potently inhibited ox-LDL-induced macrophage-derived foam cell formation, down-regulated the expression of CD36 and SRA, and up-regulated the expression of ABCA1. Atorvastatin markedly suppressed the activation of PPARγ and p-iκB in ox-LDL-stimulated THP-1 macrophages (P<0.05) and significantly decreased the Dil-oxLDL-binding capacity of the macrophages (P<0.05).
  
  
  CONCLUSIONS
  Atorvastatin as an effective anti-atherosclerosis agent can suppress the activation of PPARγ and p-iκB to reduce lipid accumulation in macrophages.
authors: Department of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.E-mail: cxfchongda@163.com.
authors: Xiaofeng
authors: X
authors: Cheng
authors: Xiaoyan
authors: X
authors: Liu
authors: Lingkun
authors: L
authors: Song
authors: Yun
authors: Y
authors: He
authors: Xiaoqing
authors: X
authors: Li
authors: Hao
authors: H
authors: Zhang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000069059:Atorvastatin; D002460:Cell Line; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D006538:Heptanoic Acids; D020672:I-kappa B Proteins; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D047495:PPAR gamma; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin