title: [The impact of cyclophilin A small interfering RNA on the formation of atherosclerotic plaque in apolipoprotein E-deficient mice].
abstract: OBJECTIVE
  The aim of this study was to determine whether inhibition of cyclophilin A by lentivirus-mediated RNA interference (RNAi) could inhibit progression of atherosclerotic plaques and increase collagen production.
  
  
  METHODS
  Atherosclerostic plaque model was induced by rapid perivascular carotid silicone collar placement in ApoE(-/-) mice. The recombinant CyPA-RNAi-Lentivirus (CyPA-RNAi-LV) or negative control-green fluorescent protein-Lentivirus (NC-GFP-LV) were constructed and transfected into right carotid plaques, respectively. Using the local injection method, ApoE(-/-) mice carotid artery plaque were intervened 10 min in the silicone collar placement with 10 µl (1.0 × 10⁸ TU/ml) lentivirus vector. The areas and CyPA expression of plaques were analyzed by morphological observation, real-time polymerase chain reaction (RT-PCR) and Western blot respectively.
  
  
  RESULTS
  CyPA-RNAi-LV not only prevented plaques progression ((9 085 ± 671) µm² to (18 021 ± 1 901) µm²), but also decreased plaque lipid content ((28.9 ± 6.3)% to (17.8 ± 4.5)%), increased plaque collagen content ((24.2 ± 4.8)% to (35.1 ± 5.2)%) at 6 weeks after lentivirus transfection. The intima/media ratio (0.36 ± 0.11 vs. 0.65 ± 0.12, P < 0.05) and degree of lumen stenosis (intima/lumen ratios, 0.18 ± 0.02 vs. 0.33 ± 0.03, P < 0.05) were also significantly reduced by CyPA-RNAi-LV. Moreover, RT-PCR analysis revealed downregulated expressions of proinflammatory cytokines and matrix metalloproteinases (MMP-9 -17.5%) in the CyPA-RNAi-LV group.
  
  
  CONCLUSIONS
  Lentivirus-mediated CyPA silencing by siRNA could inhibit plaques progression and reduce local inflammation through the anti-inflammatory effects in this model.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China. Email: yanjinchuan@hotmail.com.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University,Zhenjiang 212001, China.
authors.forename: Zhongqun
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E; D021984:Cyclophilin A / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D020868:Gene Silencing; D005822:Genetic Vectors; D007249:Inflammation; D016086:Lentivirus; D020780:Matrix Metalloproteinase 9; D020782:Matrix Metalloproteinases; D051379:Mice; D058226:Plaque, Atherosclerotic; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D001057:Apolipoproteins E; D034741:RNA, Small Interfering; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9; D021984:Cyclophilin A