Blockade of RBP-J-Mediated Notch Signaling Pathway Exacerbates Cardiac Remodeling after Infarction by Increasing Apoptosis in Mice.
Blockade of RBP-J-Mediated Notch Signaling Pathway Exacerbates Cardiac Remodeling after Infarction by Increasing Apoptosis in Mice.
复制标题
阻断 RBP-J 介导的 Notch 信号通路会增加小鼠的细胞凋亡，从而加剧梗死后的心脏重塑
DOI：
10.1155/2018/5207031
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发表时间：
2018
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
He Y;Pang S;Huang J;Zhu K;Tong J;Tang Y;Ma G;Chen L
背景缺血性心脏病（IHD）是心血管疾病患者死亡的主要原因。心肌梗死后心脏重构是一种常见的病理变化，心肌细胞凋亡在其中起着重要作用。转录因子重组信号结合蛋白-J（RBP-J）介导的Notch信号通路与包括主动脉瓣疾病在内的多种遗传性心血管疾病有关，但RBP-J介导的Notch信号通路是否在MI后心肌细胞凋亡中发挥作用尚不清楚。方法将RBP-Jfl/fl小鼠与Myh 6-Cre/Esr 1转基因小鼠杂交，体内缺失RBP-J基因，部分抑制经典的Notch信号通路。通过永久性结扎左冠状动脉前降支，然后敲除RBP-J诱导小鼠MI。心肌梗死后4周，通过超声心动图和组织学分析评估心脏功能和形态学。采用真实的时间PCR和western blot检测细胞凋亡相关分子的表达和调控。结果RBP-J基因敲除可导致小鼠存活率降低、心肌梗死后重构和功能恶化，并与心肌细胞凋亡增加有关。其机制可能与下调bcl-2表达、上调bax表达和切割型caspase 3蛋白表达，加剧心肌细胞凋亡有关。结论RBP-J介导的Notch信号通路抑制心肌梗死后心室重构，改善心功能。RBP-J介导的Notch信号通路在心脏损伤后的心肌细胞凋亡中具有保护作用。
Background Ischemic heart disease (IHD) is the major cause of death in patients with cardiovascular disease. Cardiac remodeling is a common pathological change following myocardial infarction (MI), and cardiomyocyte apoptosis plays a key role in this change. Transcription factor recombination signal-binding protein-J (RBP-J)-mediated Notch signaling pathway has been implicated in several inherited cardiovascular diseases, including aortic valve diseases, but whether the RBP-J-mediated Notch signaling pathway plays a role in cardiomyocyte apoptosis after MI is unclear. Method We crossed RBP-Jfl/fl mice and Myh6-Cre/Esr1 transgenic mice to delete RBP-J in vivo and to partly inhibit the canonical Notch signaling pathway. MI was induced in mice by permanent ligation of the left anterior descending coronary artery followed by the knockout of RBP-J. Cardiac function and morphology were assessed by echocardiography and histological analysis 4 weeks after infarction. In addition, the expression and regulation of apoptosis-related molecules were examined by real time PCR and western blot. Results RBP-J knockout decreased the survival rate and deteriorated post-MI remodeling and function in mice, and this effect was associated with increased cardiomyocyte apoptosis. The potential mechanisms might be related to the downregulated expression of bcl-2, upregulated expression of bax, and cleaved-caspase 3 to exacerbate cardiomyocyte apoptosis. Conclusion These findings show that the RBP-J-mediated Notch signaling pathway in cardiomyocytes limits ventricular remodeling and improves cardiac function after MI. The RBP-J-mediated Notch signaling pathway has a protective role in cardiomyocyte apoptosis following cardiac injury.
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影响因子：
4.4
作者：
Han, H;Tanigaki, K;Honjo, T
通讯作者：
Honjo, T
松弛素可以通过Notch1途径改善高葡萄糖诱导的心肌细胞肥大和凋亡。
影响因子：
2.7
作者：
Wei X;Yang Y;Jiang YJ;Lei JM;Guo JW;Xiao H
通讯作者：
Xiao H
影响因子：
9.3
作者：
Li, Yuxin;Hiroi, Yukio;Liao, James K.
通讯作者：
Liao, James K.
DOI：
10.1016/j.bbrc.2014.10.023
发表时间：
2014-11-07
影响因子：
3.1
作者：
Wang, Haihe;Yang, Zhanchun;Chen, Guofu
通讯作者：
Chen, Guofu
影响因子：
4.5
作者：
Ding JW;Tong XH;Yang J;Liu ZQ;Zhang Y;Yang J;Li S;Li L
通讯作者：
Li L