Endothelial Derived Neuregulin-1 may be Important for Cardioprotection Induced by Ischemic Preconditioning

Guizhen Yang, F. Xue, Chao Sun, X. Liao, Jian-hua Liu
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Abstract

Aim of review: The underlying mechanisms of ischemic preconditioning (IPC) have been studied for many years, but have not been elucidated completely. The available literatures indicate that endothelial derived neuregulin-1 (NRG-1) is involved in myocardial ischemia/reperfusion injury (IRI) and protects cardiomyocytes against H2O2-induced apoptosis by regulating endoplasmic reticulum stress (ERS). The aim of this review is to provide the evidence that endothelial derived NRG-1 maybe a crucial biomolecule mediating powerful cardioprotection by IPC.Methods: According to the available literatures, this review will first discuss the factors attributable to cardioprotection of IPC and then provide an overview of the cellular and molecular mechanisms of endothelial derived NRG-1 maybe involved in IPC induced cardioprotection.Recent findings: Multiple factors are attributable to cardioprotection induced by IPC. It has been shown that anoxia preconditioning in vitro can not provide cardioprotection as much as the IPC in vivo. During myocardial ischemic conditioning, endothelial cells may play several roles: a “receptor” for blood-borne conditioning moieties, a sensor for hypoxic stress and a paracrine organ. The NRG-1 produced by endothelial cells has been proved to protect against myocardial IRI through a PI3K/Akt pathway. Furthermore, unbalanced endoplasmic reticulum stress is one of the important mechanisms of IRI, and IPC has been demonstrated to protect myocardial IRI by regulating endoplasmic reticulum stress. In addition, NRG-1 may attenuate IRI by regulating cold inducible RNA-binding protein with its downstream endoplasmic reticulum stress related signaling pathways.Summary: Endothelial derived NRG-1 and its downstream signaling pathways are involved in multiple aspects of cardiac physiology and function, and can provide a significant protection against myocardial injury. The available evidence indicates that selective deletion of endothelial derived NRG-1 in vivo decreases the tolerance to IRI, as demonstrated by impaired recovery of post-ischemic myocardial contraction function. Thus, endothelial derived NRG-1 maybe a crucial biomolecule mediating powerful cardioprotection by IPC. If this new view is proved by basic and clinical experiments, a crucial biomolecule mediated cardioprotection induced by IPC would be revealed. Citation:  Gui-Zhen Yang, Fu-Shan Xue, Chao Sun, Xu Liao, Jian-Hua Liu. Endothelial derived neuregulin-1 may be important for cardioprotection induced by ischemic preconditioning. J Anesth Perioper Med 2017; 4: 225-30. doi: 10.24015/JAPM.2017.0008This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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内皮来源的神经调节蛋白1可能在缺血预处理诱导的心脏保护中起重要作用
综述目的:缺血预处理(IPC)的潜在机制已被研究多年,但尚未完全阐明。现有文献表明,内皮源性神经调节蛋白1 (NRG-1)参与心肌缺血/再灌注损伤(IRI),并通过调节内质网应激(ERS)保护心肌细胞免受h2o2诱导的凋亡。本文旨在为内皮源性NRG-1可能是介导IPC强大的心脏保护作用的重要生物分子提供证据。方法:根据现有文献,本文首先讨论IPC对心脏保护的影响因素,然后对内皮源性NRG-1可能参与IPC诱导心脏保护的细胞和分子机制进行综述。近期研究发现:IPC诱导的心脏保护可归因于多种因素。研究表明,体外缺氧预处理对心脏的保护作用不如体内缺氧预处理。在心肌缺血调节过程中,内皮细胞可能扮演多种角色:血源性调节部分的“受体”,缺氧应激的传感器和旁分泌器官。内皮细胞产生的NRG-1已被证明通过PI3K/Akt通路对心肌IRI具有保护作用。此外,不平衡的内质网应激是IRI的重要机制之一,IPC已被证明通过调节内质网应激来保护心肌IRI。此外,NRG-1可能通过调节冷诱导rna结合蛋白及其下游内质网应激相关信号通路来减弱IRI。摘要:内皮源性NRG-1及其下游信号通路参与心脏生理和功能的多个方面,对心肌损伤具有重要的保护作用。现有证据表明,在体内选择性删除内皮源性NRG-1会降低对IRI的耐受性,缺血后心肌收缩功能恢复受损就是证明。因此,内皮源性NRG-1可能是介导IPC强大的心脏保护作用的重要生物分子。如果这一新观点得到基础实验和临床实验的证实,IPC诱导的一个重要的生物分子介导的心脏保护机制将被揭示出来。引用本文:杨桂珍,薛福山,孙超,廖旭,刘建华。内皮源性神经调节蛋白-1可能在缺血预处理诱导的心脏保护中起重要作用。中华外科杂志2017;4: 225 - 30。doi: 10.24015/ japm .2017.0008这是一篇开放获取的文章,由Evidence Based Communications (EBC)发表。本作品遵循知识共享署名4.0国际许可协议,允许以任何媒介或格式出于任何合法目的不受限制地使用、分发和复制。要查看此许可证的副本,请访问http://creativecommons.org/licenses/by/4.0/。
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