Yuan Weihua, Zhang Xicheng, Fan Xiangming
National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, 3333 Binsheng Rd, Hangzhou 310052, China.
National Clinical Research Center for Child Health, Department of Cardiac Surgery, Children's Hospital, Zhejiang University School of Medicine, 3333 Binsheng Rd, Hangzhou 310052, China.
Curr Issues Mol Biol. 2023 Jul 13;45(7):5830-5848. doi: 10.3390/cimb45070369.
Mechanotransduction (MT) is inseparable from the pathobiology of heart failure (HF). However, the effects of mechanical forces on HF remain unclear. This review briefly describes how Piezo1 functions in HF-affected cells, including endothelial cells (ECs), cardiac fibroblasts (CFs), cardiomyocytes (CMs), and immune cells. Piezo1 is a mechanosensitive ion channel that has been extensively studied in recent years. Piezo1 responds to different mechanical forces and converts them into intracellular signals. The pathways that modulate the Piezo1 switch have also been briefly described. Experimental drugs that specifically activate Piezo1-like proteins, such as Yoda1, Jedi1, and Jedi2, are available for clinical studies to treat Piezo1-related diseases. The only mechanosensitive ion-channel-specific inhibitor available is GsMTx4, which can turn off Piezo1 by modulating the local membrane tension. Ultrasound waves can modulate Piezo1 switching in vitro with the assistance of microbubbles. This review provides new possible targets for heart failure therapy by exploring the cellular functions of Piezo1 that are involved in the progression of the disease. Modulation of Piezo1 activity may, therefore, effectively delay the progression of heart failure.
机械转导（MT）与心力衰竭（HF）的病理生物学密不可分。然而，机械力对HF的影响仍不清楚。本综述简要描述了Piezo1在受HF影响的细胞中的功能，包括内皮细胞（ECs）、心脏成纤维细胞（CFs）、心肌细胞（CMs）和免疫细胞。Piezo1是一种机械敏感离子通道，近年来已得到广泛研究。Piezo1对不同的机械力作出反应，并将其转化为细胞内信号。本文还简要描述了调节Piezo1开关的途径。有一些特异性激活Piezo1样蛋白的实验药物，如Yoda1、Jedi1和Jedi2，可用于治疗Piezo1相关疾病的临床研究。唯一可用的机械敏感离子通道特异性抑制剂是GsMTx4，它可通过调节局部膜张力来关闭Piezo1。在微泡的辅助下，超声波可在体外调节Piezo1开关。本综述通过探索Piezo1参与疾病进展的细胞功能，为心力衰竭治疗提供了新的可能靶点。因此，调节Piezo1活性可能有效延缓心力衰竭的进展。
