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Nur77 decreases atherosclerosis progression in apoE(-/-) mice fed a high-fat/high-cholesterol diet.
- Source :
-
PloS one [PLoS One] 2014 Jan 31; Vol. 9 (1), pp. e87313. Date of Electronic Publication: 2014 Jan 31 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- 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.<br />Objective: Here, we explored the role of Nur77 in atherosclerotic plaque progression in apoE(-/-) mice fed a high-fat/high cholesterol diet.<br />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.<br />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.
- Subjects :
- Animals
Apolipoproteins E genetics
Atherosclerosis etiology
Atherosclerosis genetics
Blotting, Western
Caco-2 Cells
Cell Line, Tumor
Cholesterol, Dietary adverse effects
Diet, High-Fat adverse effects
Disease Progression
Foam Cells drug effects
Foam Cells metabolism
Gene Expression drug effects
Hep G2 Cells
Humans
Inflammation genetics
Inflammation metabolism
Lipid Metabolism drug effects
Liver drug effects
Liver metabolism
Liver pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nuclear Receptor Subfamily 4, Group A, Member 1 agonists
Nuclear Receptor Subfamily 4, Group A, Member 1 genetics
Phenylacetates pharmacology
Plaque, Atherosclerotic etiology
Plaque, Atherosclerotic genetics
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Apolipoproteins E metabolism
Atherosclerosis metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1 metabolism
Plaque, Atherosclerotic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24498071
- Full Text :
- https://doi.org/10.1371/journal.pone.0087313