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Nur77 Decreases Atherosclerosis Progression in apoE(−/−) Mice Fed a High-Fat/High-Cholesterol Diet
RATIONALE: It is clear that lipid disorder and inflammation are associated with cardiovascular diseases and underlying atherosclerosis. Nur77 has been shown to be involved in inflammatory response and lipid metabolism. OBJECTIVE: Here, we explored the role of Nur77 in atherosclerotic plaque progress...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909091/ https://www.ncbi.nlm.nih.gov/pubmed/24498071 http://dx.doi.org/10.1371/journal.pone.0087313 |
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author | Hu, Yan-Wei Zhang, Peng Yang, Jun-Yao Huang, Jin-Lan Ma, Xin Li, Shu-Fen Zhao, Jia-Yi Hu, Ya-Rong Wang, Yan-Chao Gao, Ji-Juan Sha, Yan-Hua Zheng, Lei Wang, Qian |
author_facet | Hu, Yan-Wei Zhang, Peng Yang, Jun-Yao Huang, Jin-Lan Ma, Xin Li, Shu-Fen Zhao, Jia-Yi Hu, Ya-Rong Wang, Yan-Chao Gao, Ji-Juan Sha, Yan-Hua Zheng, Lei Wang, Qian |
author_sort | Hu, Yan-Wei |
collection | PubMed |
description | RATIONALE: It is clear that lipid disorder and inflammation are associated with cardiovascular diseases and underlying atherosclerosis. Nur77 has been shown to be involved in inflammatory response and lipid metabolism. OBJECTIVE: Here, we explored the role of Nur77 in atherosclerotic plaque progression in apoE(−/−) mice fed a high-fat/high cholesterol diet. METHODS AND RESULTS: The Nur77 gene, a nuclear hormone receptor, was highly induced by treatment with Cytosporone B (Csn-B, specific Nur77 agonist), recombinant plasmid over-expressing Nur77 (pcDNA-Nur77), while inhibited by treatment with siRNAs against Nur77 (si-Nur77) in THP-1 macrophage-derived foam cells, HepG2 cells and Caco-2 cells, respectively. In addition, the expression of Nur77 was highly induced by Nur77 agonist Csn-B, lentivirus encoding Nur77 (LV-Nur77), while silenced by lentivirus encoding siRNA against Nur77 (si-Nur77) in apoE(−/−) mice fed a high-fat/high cholesterol diet, respectively. We found that increased expression of Nur77 reduced macrophage-derived foam cells formation and hepatic lipid deposition, downregulated gene levels of inflammatory molecules, adhesion molecules and intestinal lipid absorption, and decreases atherosclerotic plaque formation. CONCLUSION: These observations provide direct evidence that Nur77 is an important nuclear hormone receptor in regulation of atherosclerotic plaque formation and thus represents a promising target for the treatment of atherosclerosis. |
format | Online Article Text |
id | pubmed-3909091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39090912014-02-04 Nur77 Decreases Atherosclerosis Progression in apoE(−/−) Mice Fed a High-Fat/High-Cholesterol Diet Hu, Yan-Wei Zhang, Peng Yang, Jun-Yao Huang, Jin-Lan Ma, Xin Li, Shu-Fen Zhao, Jia-Yi Hu, Ya-Rong Wang, Yan-Chao Gao, Ji-Juan Sha, Yan-Hua Zheng, Lei Wang, Qian PLoS One Research Article RATIONALE: It is clear that lipid disorder and inflammation are associated with cardiovascular diseases and underlying atherosclerosis. Nur77 has been shown to be involved in inflammatory response and lipid metabolism. OBJECTIVE: Here, we explored the role of Nur77 in atherosclerotic plaque progression in apoE(−/−) mice fed a high-fat/high cholesterol diet. METHODS AND RESULTS: The Nur77 gene, a nuclear hormone receptor, was highly induced by treatment with Cytosporone B (Csn-B, specific Nur77 agonist), recombinant plasmid over-expressing Nur77 (pcDNA-Nur77), while inhibited by treatment with siRNAs against Nur77 (si-Nur77) in THP-1 macrophage-derived foam cells, HepG2 cells and Caco-2 cells, respectively. In addition, the expression of Nur77 was highly induced by Nur77 agonist Csn-B, lentivirus encoding Nur77 (LV-Nur77), while silenced by lentivirus encoding siRNA against Nur77 (si-Nur77) in apoE(−/−) mice fed a high-fat/high cholesterol diet, respectively. We found that increased expression of Nur77 reduced macrophage-derived foam cells formation and hepatic lipid deposition, downregulated gene levels of inflammatory molecules, adhesion molecules and intestinal lipid absorption, and decreases atherosclerotic plaque formation. CONCLUSION: These observations provide direct evidence that Nur77 is an important nuclear hormone receptor in regulation of atherosclerotic plaque formation and thus represents a promising target for the treatment of atherosclerosis. Public Library of Science 2014-01-31 /pmc/articles/PMC3909091/ /pubmed/24498071 http://dx.doi.org/10.1371/journal.pone.0087313 Text en © 2014 Hu 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hu, Yan-Wei Zhang, Peng Yang, Jun-Yao Huang, Jin-Lan Ma, Xin Li, Shu-Fen Zhao, Jia-Yi Hu, Ya-Rong Wang, Yan-Chao Gao, Ji-Juan Sha, Yan-Hua Zheng, Lei Wang, Qian Nur77 Decreases Atherosclerosis Progression in apoE(−/−) Mice Fed a High-Fat/High-Cholesterol Diet |
title | Nur77 Decreases Atherosclerosis Progression in apoE(−/−) Mice Fed a High-Fat/High-Cholesterol Diet |
title_full | Nur77 Decreases Atherosclerosis Progression in apoE(−/−) Mice Fed a High-Fat/High-Cholesterol Diet |
title_fullStr | Nur77 Decreases Atherosclerosis Progression in apoE(−/−) Mice Fed a High-Fat/High-Cholesterol Diet |
title_full_unstemmed | Nur77 Decreases Atherosclerosis Progression in apoE(−/−) Mice Fed a High-Fat/High-Cholesterol Diet |
title_short | Nur77 Decreases Atherosclerosis Progression in apoE(−/−) Mice Fed a High-Fat/High-Cholesterol Diet |
title_sort | nur77 decreases atherosclerosis progression in apoe(−/−) mice fed a high-fat/high-cholesterol diet |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909091/ https://www.ncbi.nlm.nih.gov/pubmed/24498071 http://dx.doi.org/10.1371/journal.pone.0087313 |
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