title: Role of Krüppel-like factor 2 and protease-activated receptor-1 in vulnerable plaques of ApoE(-/-) mice and intervention with statin.
abstract: BACKGROUND
  Krüppel-like factor 2 (KLF2) and protease-activated receptor-1 (PAR-1) are 2 novel factors that play important roles in inflammation and coagulation, yet their relationship with vulnerable plaques and statin remains uncertain. The purpose of this study was to explore the expression of KLF2 and PAR-1 in vulnerable plaques of ApoE gene knockout (ApoE(-/-)) mice and the pharmaceutical effect of statin on the expression of KLF2 and PAR-1.
  
  
  METHODS
  ApoE(-/-) mice were randomized into an early-treatment group and a late-treatment group. Each group was randomized into 4 subgroups: normal diet control, high-fat diet control, high-dose statin, and low-dose statin. After 8 weeks of intervention with statin, the aortas were harvested to determine KLF2 and PAR-1 expression by semiquantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical analyses. The relative area of plaque, the ratio of fibrous cap thickness to tunica intima/media thickness, and the vulnerability index of atherosclerotic plaques were calculated to evaluate plaque vulnerability.
  
  
  RESULTS
  KLF2 increased whereas PAR-1 decreased in vulnerable plaques at messenger RNA, protein, and histologic levels. Atorvastatin increased KLF2 and decreased PAR-1 expression.
  
  
  CONCLUSIONS
  Plaque vulnerability correlated negatively with KLF2 but positively with PAR-1. Upregulation of KLF2 and downregulation of PAR-1 could be direct or indirect effects of statin therapy.
authors: Department of Cardiology, Kunming General Hospital of Chengdu Military Command, Yunnan, China. doctorlxyang@163.com
authors: Lixia
authors: L
authors: Yang
authors: Xiaobin
authors: X
authors: Zhou
authors: Ruiwei
authors: R
authors: Guo
authors: Yankun
authors: Y
authors: Shi
authors: Xing
authors: X
authors: Liang
authors: Xuhua
authors: X
authors: Heng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D000069059:Atorvastatin; D015153:Blotting, Western; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000473:pathology; D011758:Pyrroles / Q000627:therapeutic use*; D044463:Receptor, PAR-1 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D011758:Pyrroles; D044463:Receptor, PAR-1; D000069059:Atorvastatin