cytosporone-b and Atherosclerosis

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.. Here, we explored the role of Nur77 in atherosclerotic plaque progression in apoE(-/-) mice fed a high-fat/high cholesterol diet.. 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.. 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.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Blotting, Western; Caco-2 Cells; Cell Line, Tumor; Cholesterol, Dietary; Diet, High-Fat; Disease Progression; Foam Cells; Gene Expression; Hep G2 Cells; Humans; Inflammation; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Receptor Subfamily 4, Group A, Member 1; Phenylacetates; Plaque, Atherosclerotic; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference