Quinn Julianna N, Wang Jun
Department of Pediatrics, McGovern Medical School at UTHealth, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
McGovern Medical School at UTHealth, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Int J Drug Discov Pharm. 2023;2(4):36-43. doi: 10.53941/ijddp.2023.100014. Epub 2023 Dec 26.
The cardiac conduction system (CCS) propagates electrical impulses, generates cardiac contractions, and ultimately ensures regular heartbeats. Disruptions within the CCS lead to cardiac arrhythmias, which are known to be the leading cause of cardiac-related mortalities in humans. The sinoatrial node (SAN) is a key component of the CCS and functions as the natural cardiac pacemaker to initiate normal cardiac impulse and conduction. The SAN is characterized by significant heterogeneity and contains various cell types, including pacemaker cells that spontaneously generate action potentials to maintain a constant beating rhythm. The fundamental Hippo signaling pathway plays a key role in heart development and regeneration. Recently, the Hippo signaling pathway is indicated as a critical pathway for maintaining SAN homeostasis, suggesting therapeutic targets for SAN disorders. This mini-review focuses on the recent molecular and mechanistic findings of Hippo's involvement in regulating SAN homeostasis and discusses potential new therapeutic targets for SAN pathologies.
心脏传导系统(CCS)可传导电冲动,引发心脏收缩,并最终确保心跳规律。CCS内的紊乱会导致心律失常,而心律失常是已知的人类心脏相关死亡的主要原因。窦房结(SAN)是CCS的关键组成部分,作为天然心脏起搏器发挥作用,启动正常的心脏冲动和传导。SAN具有显著的异质性,包含多种细胞类型,包括能自发产生动作电位以维持恒定搏动节律的起搏细胞。基础的Hippo信号通路在心脏发育和再生中起关键作用。最近,Hippo信号通路被表明是维持SAN稳态的关键通路,提示了针对SAN疾病的治疗靶点。本综述聚焦于Hippo参与调节SAN稳态的最新分子和机制研究发现,并讨论了SAN病理的潜在新治疗靶点。