Nur77 decreases atherosclerosis progression in apoE(-/-) mice fed a high-fat/high-cholesterol diet.
Nur77 decreases atherosclerosis progression in apoE(-/-) mice fed a high-fat/high-cholesterol diet.
复制标题
DOI：
10.1371/journal.pone.0087313
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Hu YW;Zhang P;Yang JY;Huang JL;Ma X;Li SF;Zhao JY;Hu YR;Wang YC;Gao JJ;Sha YH;Zheng L;Wang Q
很明显，脂质紊乱和炎症与心血管疾病和潜在的动脉粥样硬化有关。Nur 77已被证明参与炎症反应和脂质代谢。在这里，我们探讨了Nur 77在高脂肪/高胆固醇饮食apoE−/−小鼠动脉粥样硬化斑块进展中的作用。在THP-1巨噬细胞源性泡沫细胞、HepG 2细胞和Caco-2细胞中，Nur 77基因分别被Cytosporone B（Csn-B，特异性Nur 77激动剂）、过表达Nur 77的重组质粒（pcDNA-Nur 77）诱导表达，而被针对Nur 77的siRNA（si-Nur 77）抑制。此外，Nur 77的表达被Nur 77激动剂Csn-B，编码Nur 77的慢病毒（LV-Nur 77）高度诱导，而在喂食高脂肪/高胆固醇饮食的apoE−/−小鼠中，Nur 77的表达被编码针对Nur 77的siRNA的慢病毒（si-Nur 77）沉默。我们发现Nur 77表达增加可减少巨噬细胞源性泡沫细胞形成和肝脏脂质沉积，下调炎症分子、粘附分子和肠道脂质吸收的基因水平，并减少动脉粥样硬化斑块形成。这些观察结果提供了直接的证据，Nur 77是一个重要的核激素受体在调节动脉粥样硬化斑块的形成，因此代表了一个有前途的目标，用于治疗动脉粥样硬化。
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.
登录
查看更多内容
影响因子：
4.8
作者：
Davis, HR;Zhu, LJ;Altmann, SW
通讯作者：
Altmann, SW
DOI：
10.1152/ajpgi.00061.2008
发表时间：
2008-04-01
影响因子：
4.5
作者：
Hui, David Y.;Labonte, Eric D.;Howles, Philip N.
通讯作者：
Howles, Philip N.
影响因子：
20.1
作者：
Hamers, Anouk A. J.;Vos, Mariska;de Vries, Carlie J. M.
通讯作者：
de Vries, Carlie J. M.
影响因子：
56.9
作者：
Altmann, SW;Davis, HR;Graziano, MP
通讯作者：
Graziano, MP
DOI：
10.1161/01.atv.0000238346.84458.5d
发表时间：
2006-10-01
影响因子：
8.7
作者：
Bonta, Peter I.;van Tiel, Claudia M.;de Vries, Carlie J. M.
通讯作者：
de Vries, Carlie J. M.