Hu Xu, Van Marion Denise M S, Wiersma Marit, Zhang Deli, Brundel Bianca J J M
Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Cell Stress Chaperones. 2017 Jul;22(4):665-674. doi: 10.1007/s12192-017-0799-4. Epub 2017 May 8.
Atrial fibrillation (AF) is the most common tachyarrhythmia which is associated with increased morbidity and mortality. AF usually progresses from a self-terminating paroxysmal to persistent disease. It has been recognized that AF progression is driven by structural remodeling of cardiomyocytes, which results in electrical and contractile dysfunction of the atria. We recently showed that structural remodeling is rooted in derailment of proteostasis, i.e., homeostasis of protein production, function, and degradation. Since heat shock proteins (HSPs) play an important role in maintaining a healthy proteostasis, the role of HSPs was investigated in AF. It was found that especially small heat shock protein (HSPB) levels get exhausted in atrial tissue of patients with persistent AF and that genetic or pharmacological induction of HSPB protects against cardiomyocyte remodeling in experimental models for AF. In this review, we provide an overview of HSPBs as a potential therapeutic target for normalizing proteostasis and suppressing the substrates for AF progression in experimental and clinical AF and discuss HSP activators as a promising therapy to prevent AF onset and progression.
心房颤动（AF）是最常见的快速性心律失常，与发病率和死亡率增加相关。AF通常从自限性阵发性发展为持续性疾病。人们已经认识到，AF的进展是由心肌细胞的结构重塑驱动的，这导致心房的电功能和收缩功能障碍。我们最近发现，结构重塑源于蛋白质稳态的失调，即蛋白质产生、功能和降解的稳态。由于热休克蛋白（HSPs）在维持健康的蛋白质稳态中起重要作用，因此研究了HSPs在AF中的作用。研究发现，尤其是小分子热休克蛋白（HSPB）水平在持续性AF患者的心房组织中耗尽，并且在AF实验模型中，HSPB的基因或药理学诱导可防止心肌细胞重塑。在本综述中，我们概述了HSPBs作为使蛋白质稳态正常化和抑制AF在实验性和临床性AF中进展的底物的潜在治疗靶点，并讨论了HSP激活剂作为预防AF发生和进展的有前景疗法。
