Rev-erb agonist improves adverse cardiac remodeling and survival in myocardial infarction through an anti-inflammatory mechanism.
Rev-erb agonist improves adverse cardiac remodeling and survival in myocardial infarction through an anti-inflammatory mechanism.
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DOI：
10.1371/journal.pone.0189330
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Aonuma K
中科院分区：
文献类型：
--
作者：
Stujanna EN;Murakoshi N;Tajiri K;Xu D;Kimura T;Qin R;Feng D;Yonebayashi S;Ogura Y;Yamagami F;Sato A;Nogami A;Aonuma K
Rev-erb α被称为核受体1D 1（NR 1D 1），调节昼夜节律、调节糖和脂代谢以及炎症反应。然而，关于Rev-erb激动剂对心肌梗死（MI）和心力衰竭进展的影响知之甚少。为探讨这一点，野生型雄性小鼠进行假手术或永久性结扎左冠状动脉前降支建立MI模型。腹膜内给予Rev-erb激动剂SR9009（100 mg/kg/天）或溶媒。术后1周行超声心动图评价心功能。采用实时荧光定量PCR、免疫印迹和免疫荧光法检测左心室（LV）中基因和蛋白质的表达水平。此外，通过流式细胞术分析免疫细胞向LV中的浸润。MI后用SR9009治疗显著改善了存活率和降低的LV功能。在用SR9009（MI+SR）处理的MI小鼠中，脑利钠肽的表达水平和血浆浓度显著低于用媒介物（MI+V）处理的MI小鼠。此外，MI+SR中炎症相关分子如IL 6、Mcp 1、Ly 6 g、Cd 11 B b、基质金属肽酶（Mmp）9的mRNA表达水平以及磷酸化NF-κB p65、磷酸化ERK和磷酸化p38的蛋白表达水平也显著低于MI+ V。而心肌梗死+SR组显著低于心肌梗死+V组。心肌梗死+V组左室中性粒细胞和促炎性巨噬细胞浸润显著增加，心肌梗死+SR组显著抑制。
Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered. Echocardiography was performed to evaluate cardiac function 1 week after surgery. The gene and protein expression levels in the left ventricles (LVs) were determined with real-time PCR, western blotting, and immunofluorescence. Moreover, immune cell infiltration into the LVs was analyzed by flow cytometry. Survival rate and reduced LV function were significantly improved by the treatment with SR9009 after MI. The expression level and plasma concentration of brain natriuretic peptide were significantly lower in MI mice treated with SR9009 (MI+SR) than in MI mice treated with vehicle (MI+V). Moreover, the mRNA expression levels of inflammatory-related molecules such as Il6, Mcp1, Ly6g, Cd11b, matrix metallopeptidase (Mmp)9, and the protein expression levels of phosphorylated NF-κB p65, phosphorylated ERK, and phosphorylated p38 were also significantly lower in MI+SR than in MI+V. Immunofluorescence intensity for MMP-9 was enhanced in the LVs, but was less so in MI+SR than in MI+V. Furthermore, infiltrations of neutrophils and proinflammatory macrophages in the LVs were dramatically increased in MI+V and were significantly suppressed in MI+SR. Rev-erb agonist SR9009 treatment inhibited post-MI mortality and improved cardiac function through modulating inflammation and remodeling process.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.4331/wjbc.v1.i5.69
发表时间：
2010-05-26
期刊：
World journal of biological chemistry
影响因子：
--
作者：
Matsui, Yutaka;Morimoto, Junko;Uede, Toshimitsu
通讯作者：
Uede, Toshimitsu
影响因子：
6.5
作者：
Raspé, E;Duez, H;Staels, B
通讯作者：
Staels, B
DOI：
10.1073/pnas.1106750109
发表时间：
2012-01-10
影响因子：
11.1
作者：
Gibbs, Julie E.;Blaikley, John;Loudon, Andrew S. I.
通讯作者：
Loudon, Andrew S. I.
影响因子：
4.4
作者：
Yang, Fang;Inoue, Ikuo;Ikeda, Masaaki
通讯作者：
Ikeda, Masaaki