title: Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice.
abstract: OBJECTIVE
  Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored.
  
  
  METHODS
  In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E-deficient (ApoE-/-) mice, and lentivirus expressing visfatin (lenti-visfatin) was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC) and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated.
  
  
  RESULTS
  Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP-2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-κB, and inhibition of NF-κB significantly reduced visfatin-induced MMP-8 production.
  
  
  CONCLUSIONS
  Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index.
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Bo
authors: B
authors: Li
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Yunhe
authors: Y
authors: Zhao
authors: Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, PR China.
authors: Hui
authors: H
authors: Liu
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Bin
authors: B
authors: Meng
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Jitao
authors: J
authors: Wang
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Tianjun
authors: T
authors: Qi
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Hui
authors: H
authors: Zhang
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Tao
authors: T
authors: Li
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Peiqing
authors: P
authors: Zhao
authors: Department of Cardiology, Central Hospital of Zibo, Zibo, PR China.
authors: Hui
authors: H
authors: Sun
authors: Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, PR China.
authors: Jia
authors: J
authors: Xu
authors: Prenatal Diagnosis Center, Zibo Maternal and Child Health Hospital, Zibo, PR China.
authors: Haibo
authors: H
authors: Song
authors: Department of Cardiology, China-Japan Friendship Hospital, Chaoyang District, Beijing, China.
authors: Zhe
authors: Z
authors: Dong
authors: Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, PR China.
authors: Fengshuang
authors: F
authors: An
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020784:Matrix Metalloproteinase 8 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D008055:Lipids; D016328:NF-kappa B; D003094:Collagen; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; C576328:MMP8 protein, mouse; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse