心脏β-肾上腺素受体调控线粒体功能在心力衰竭中的研究进展
Cardiac β-adrenergic receptor regulation of mitochondrial function in heart failure
刘爱明 1徐文丽 2肖晗 1董尔丹1
作者信息
- 1. 北京大学第三医院心内科、血管医学研究所;血管稳态与重构全国重点实验室(北京大学);北京大学临床医学高等研究院;国家卫生健康委心血管分子生物学与调节肽重点实验室;心血管受体研究北京市重点实验室,北京 100191
- 2. 康复大学青岛医院(青岛市市立医院)心肺康复研究中心;康复大学生命科学与健康学院,青岛 266113
- 折叠
摘要
β-肾上腺素受体(β-adrenergic receptor,β-AR)的异常激活以及线粒体功能障碍是促进心力衰竭发生、发展的重要病理因素.心力衰竭时,β-AR及下游信号通路的过度激活介导心肌细胞氧化应激、钙超载、代谢异常等关键病理过程,进而引起心脏炎症、心肌细胞凋亡及坏死.线粒体作为心肌细胞能量及物质代谢的核心细胞器,其数目及功能的稳态亦与细胞内钙离子水平、氧化还原平衡及信号转导密切相关.适度激活的β-AR信号通路有利于线粒体稳态的维持,介导心肌细胞正常生理功能的发挥.然而,心力衰竭时异常激活的β-AR及下游信号通路通过多种途径介导线粒体功能障碍.因此,本综述阐述β-AR及下游信号通路对线粒体的调控,以期揭示交感应激下线粒体异常所介导的氧化应激、细胞凋亡及坏死、代谢紊乱在心力衰竭中的作用,为心力衰竭的防治提供新的思路和治疗靶点.
Abstract
Heart failure is characterized by abnormal β-adrenergic receptor(β-AR)activation and mitochondrial dysfunction.In heart failure,overactivation of β-AR mediates key pathological processes in cardiomyocytes,including oxidative stress,calcium overload and metabolic abnormalities,which subsequently lead to inflammation,myocardial apoptosis and necrosis.Mitochondria are the core organelles for energy metabolism,and also play a vital role in calcium homeostasis,redox balance and signaling transduction.Moderate β-AR activation is conducive to maintaining mitochondrial homeostasis and physiological cardiomyocyte function.However,β-AR overactivation in heart failure disrupts mitochondrial function through multiple mechanisms.Therefore,our review aims to elucidate how β-AR regulates mitochondrial function,particularly under sympathetic stress,impacting oxidative stress,apoptosis,necrosis,and metabolic imbalance.By describing these mechanisms,we seek to propose new insights and therapeutic targets for the prevention and treatment of heart failure.
关键词
β-肾上腺素受体/线粒体稳态/氧化应激/凋亡/坏死/代谢Key words
β-adrenergic receptor/mitochondrial homeostasis/oxidative stress/apoptosis/necrosis/metabolism引用本文复制引用
出版年
2024
NETL
NSTL
万方数据