Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice.
OBJECTIVES: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 ex...
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doaj-4b5856eae88844cc9f5e626e8143bb432020-11-25T01:58:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014827310.1371/journal.pone.0148273Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice.Bo LiYunhe ZhaoHui LiuBin MengJitao WangTianjun QiHui ZhangTao LiPeiqing ZhaoHui SunJia XuHaibo SongZhe DongFengshuang AnOBJECTIVES: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.http://europepmc.org/articles/PMC4743838?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bo Li Yunhe Zhao Hui Liu Bin Meng Jitao Wang Tianjun Qi Hui Zhang Tao Li Peiqing Zhao Hui Sun Jia Xu Haibo Song Zhe Dong Fengshuang An |
spellingShingle |
Bo Li Yunhe Zhao Hui Liu Bin Meng Jitao Wang Tianjun Qi Hui Zhang Tao Li Peiqing Zhao Hui Sun Jia Xu Haibo Song Zhe Dong Fengshuang An Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice. PLoS ONE |
author_facet |
Bo Li Yunhe Zhao Hui Liu Bin Meng Jitao Wang Tianjun Qi Hui Zhang Tao Li Peiqing Zhao Hui Sun Jia Xu Haibo Song Zhe Dong Fengshuang An |
author_sort |
Bo Li |
title |
Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice. |
title_short |
Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice. |
title_full |
Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice. |
title_fullStr |
Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice. |
title_full_unstemmed |
Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice. |
title_sort |
visfatin destabilizes atherosclerotic plaques in apolipoprotein e-deficient mice. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
OBJECTIVES: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. |
url |
http://europepmc.org/articles/PMC4743838?pdf=render |
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