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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 lentiviru...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743838/ https://www.ncbi.nlm.nih.gov/pubmed/26848572 http://dx.doi.org/10.1371/journal.pone.0148273 |
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author | Li, Bo Zhao, Yunhe Liu, Hui Meng, Bin Wang, Jitao Qi, Tianjun Zhang, Hui Li, Tao Zhao, Peiqing Sun, Hui Xu, Jia Song, Haibo Dong, Zhe An, Fengshuang |
author_facet | Li, Bo Zhao, Yunhe Liu, Hui Meng, Bin Wang, Jitao Qi, Tianjun Zhang, Hui Li, Tao Zhao, Peiqing Sun, Hui Xu, Jia Song, Haibo Dong, Zhe An, Fengshuang |
author_sort | Li, Bo |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-4743838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47438382016-02-11 Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E–Deficient Mice Li, Bo Zhao, Yunhe Liu, Hui Meng, Bin Wang, Jitao Qi, Tianjun Zhang, Hui Li, Tao Zhao, Peiqing Sun, Hui Xu, Jia Song, Haibo Dong, Zhe An, Fengshuang PLoS One Research Article 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. Public Library of Science 2016-02-05 /pmc/articles/PMC4743838/ /pubmed/26848572 http://dx.doi.org/10.1371/journal.pone.0148273 Text en © 2016 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Li, Bo Zhao, Yunhe Liu, Hui Meng, Bin Wang, Jitao Qi, Tianjun Zhang, Hui Li, Tao Zhao, Peiqing Sun, Hui Xu, Jia Song, Haibo Dong, Zhe An, Fengshuang Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E–Deficient Mice |
title | 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_short | Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E–Deficient Mice |
title_sort | visfatin destabilizes atherosclerotic plaques in apolipoprotein e–deficient mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743838/ https://www.ncbi.nlm.nih.gov/pubmed/26848572 http://dx.doi.org/10.1371/journal.pone.0148273 |
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