Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Cardiac Electrophysiology Unit, Cardiovascular Analytics Group, Hong Kong, China.
Cells. 2022 Dec 30;12(1):151. doi: 10.3390/cells12010151.
Heat shock proteins (HSPs) are endogenous protective proteins and biomarkers of cell stress response, of which examples are HSP70, HSP60, HSP90, and small HSPs (HSPB). HSPs protect cells and organs, especially the cardiovascular system, against harmful and cytotoxic conditions. More recent attention has focused on the roles of HSPs in the irreversible remodeling of atrial fibrillation (AF), which is the most common arrhythmia in clinical practice and a significant contributor to mortality. In this review, we investigated the relationship between HSPs and atrial remodeling mechanisms in AF. PubMed was searched for studies using the terms "Heat Shock Proteins" and "Atrial Fibrillation" and their relevant abbreviations up to 10 July 2022. The results showed that HSPs have cytoprotective roles in atrial cardiomyocytes during AF by promoting reverse electrical and structural remodeling. Heat shock response (HSR) exhaustion, followed by low levels of HSPs, causes proteostasis derailment in cardiomyocytes, which is the basis of AF. Furthermore, potential implications of HSPs in the management of AF are discussed in detail. HSPs represent reliable biomarkers for predicting and staging AF. HSP inducers may serve as novel therapeutic modalities in postoperative AF. HSP induction, either by geranylgeranylacetone (GGA) or by other compounds presently in development, may therefore be an interesting new approach for upstream therapy for AF, a strategy that aims to prevent AF whilst minimizing the ventricular proarrhythmic risks of traditional anti-arrhythmic agents.
热休克蛋白（HSPs）是细胞应激反应的内源性保护蛋白和生物标志物，其中包括 HSP70、HSP60、HSP90 和小 HSP（HSPB）。HSPs 可保护细胞和器官，尤其是心血管系统，免受有害和细胞毒性的影响。最近，人们越来越关注 HSPs 在心房颤动（AF）不可逆转重构中的作用，AF 是临床实践中最常见的心律失常，也是导致死亡率升高的重要因素。在本综述中，我们研究了 HSPs 与 AF 中心房重构机制之间的关系。通过使用术语“热休克蛋白”和“心房颤动”及其相关缩写词，在 PubMed 上搜索截至 2022 年 7 月 10 日的研究。结果表明，HSPs 在 AF 期间通过促进反向电重构和结构重构，在心房肌细胞中发挥细胞保护作用。热休克反应（HSR）衰竭，随后 HSP 水平降低，导致心肌细胞中的蛋白稳态脱轨，这是 AF 的基础。此外，还详细讨论了 HSPs 在 AF 管理中的潜在意义。HSPs 是预测和分期 AF 的可靠生物标志物。HSP 诱导剂可能成为术后 AF 的新型治疗方法。因此，通过 geranylgeranylacetone（GGA）或其他目前正在开发的化合物诱导 HSP 可能是一种有趣的 AF 上游治疗新方法，这种策略旨在预防 AF 的同时，最大限度地降低传统抗心律失常药物的心室致心律失常风险。
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