Institute of Geriatric Cardiovascular Disease, Medical School of Chinese People's Liberation Army, China.
Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, USA.
Oxid Med Cell Longev. 2021 Mar 26;2021:5529810. doi: 10.1155/2021/5529810. eCollection 2021.
Impaired function of the endoplasmic reticulum (ER) is followed by evolutionarily conserved cell stress responses, which are employed by cells, including cardiomyocytes, to maintain and/or restore ER homeostasis. ER stress activates the unfolded protein response (UPR) to degrade and remove abnormal proteins from the ER lumen. Although the UPR is an intracellular defense mechanism to sustain cardiomyocyte viability and heart function, excessive activation initiates ER-dependent cardiomyocyte apoptosis. Myocardial ischemia/reperfusion (I/R) injury is a pathological process occurring during or after revascularization of ischemic myocardium. Several molecular mechanisms contribute to the pathogenesis of cardiac I/R injury. Due to the dual protective/degradative effects of ER stress on cardiomyocyte viability and function, it is of interest to understand the basic concepts, regulatory signals, and molecular processes involved in ER stress following myocardial I/R injury. In this review, therefore, we present recent findings related to the novel components of ER stress activation. The complex effects of ER stress and whether they mitigate or exacerbate myocardial I/R injury are summarized to serve as the basis for research into potential therapies for cardioprotection through control of ER homeostasis.
内质网 (ER) 功能障碍会引发进化上保守的细胞应激反应，包括心肌细胞在内的细胞会利用这些反应来维持和/或恢复 ER 稳态。ER 应激会激活未折叠蛋白反应 (UPR)，从而降解和清除 ER 腔中的异常蛋白。尽管 UPR 是一种维持心肌细胞活力和心脏功能的细胞内防御机制，但过度激活会引发 ER 依赖性心肌细胞凋亡。心肌缺血/再灌注 (I/R) 损伤是发生在缺血心肌再血管化过程中或之后的一种病理过程。几种分子机制促成了心脏 I/R 损伤的发病机制。由于 ER 应激对心肌细胞活力和功能具有双重保护/降解作用，因此了解心肌 I/R 损伤后 ER 应激的基本概念、调节信号和分子过程很有意义。因此，在这篇综述中，我们介绍了与 ER 应激激活的新成分相关的最新发现。总结了 ER 应激的复杂影响，以及它们是减轻还是加重心肌 I/R 损伤，为通过控制 ER 稳态研究潜在的心脏保护治疗方法奠定了基础。
