Notch 信号通路的激活有助于缺血预处理和后处理提供的心脏保护。

Notch signaling activation contributes to cardioprotection provided by ischemic preconditioning and postconditioning.

机构信息

Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China.

出版信息

J Transl Med. 2013 Oct 8;11:251. doi: 10.1186/1479-5876-11-251.

BACKGROUND

Notch signaling is known to be activated following myocardial ischemia, but its role in cardioprotection provided by ischemic preconditioning (IPC) and ischemic postconditioning (IPost) remains unclear.

METHODS

Lentiviral vectors were constructed to overexpress or knockdown N1ICD in H9c2 cardiomyocyte and rat heart exposed to ischemia reperfusion injury (IRI), IPC or IPost.

RESULTS

Notch1 signaling was activated during myocardial IPC and IPost, and could enhance cell viability and inhibit apoptosis. Furthermore, activated Notch1 signaling stabilized mitochondrial membrane potential and reduced reactive oxygen species induced by IRI. The cardioprotection provided by activated Notch1 signaling resembled that of IPC and IPost, which was related to Stat3 activation and regulation of apoptosis related proteins. Furthermore, in langendorff heart perfusion model, activated Notch1 signaling restored cardiac function, decreased lactate dehydrogenase release and limited infarct size after myocardial ischemia.

CONCLUSIONS

Notch1 signaling is activated and mediates cardioprotection provided by IPC and Ipost. Notch1 signaling may represent a potential new pharmacologic mimic for cardioprotection of ischemic heart disease.

背景

已知 Notch 信号在心肌缺血后被激活，但它在缺血预处理 (IPC) 和缺血后处理 (IPost) 提供的心脏保护中的作用尚不清楚。

方法

构建慢病毒载体过表达或敲低 H9c2 心肌细胞和暴露于缺血再灌注损伤 (IRI)、IPC 或 IPost 的大鼠心脏中的 N1ICD。

结果

Notch1 信号在心肌 IPC 和 IPost 期间被激活，并能增强细胞活力并抑制细胞凋亡。此外，激活的 Notch1 信号稳定了线粒体膜电位并减少了 IRI 诱导的活性氧。激活的 Notch1 信号提供的心脏保护类似于 IPC 和 IPost，这与 Stat3 的激活和凋亡相关蛋白的调节有关。此外，在 Langendorff 心脏灌流模型中，激活的 Notch1 信号恢复了心脏功能，减少了乳酸脱氢酶的释放，并限制了心肌缺血后的梗死面积。