Circadian Mechanisms: Cardiac Ion Channel Remodeling and Arrhythmias.
Circadian Mechanisms: Cardiac Ion Channel Remodeling and Arrhythmias.
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DOI：
10.3389/fphys.2020.611860
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发表时间：
2020
影响因子：
4
通讯作者：
Aromolaran AS
中科院分区：
文献类型：
--
作者：
Bernardi J;Aromolaran KA;Zhu H;Aromolaran AS
昼夜节律参与了包括心脏在内的不同组织的许多生理和病理过程。昼夜节律在不利的心功能中发挥关键作用，涉及心力衰竭和心源性猝死，突出了昼夜节律机制对健康和疾病中正常窦性节律的重要贡献。心律失常是心力衰竭患者发病和死亡的主要原因，仅在美国每年就可能导致25万人死亡；然而，人们对其分子机制知之甚少。这表明有必要提高我们目前对增加心律失常易感性的潜在分子机制的理解。肥胖及其相关病理，包括糖尿病，已经成为危险的疾病条件，易导致不良的心脏电重构导致致命的心律失常。肥胖和糖尿病的日益流行表明患者对心律失常的易感性仍将很高。一个重要的目标是确定调节肥胖和/或糖尿病的新的和未被认识的细胞机制或信号通路。在这篇综述中，我们讨论了代谢和环境线索的昼夜节律控制，心脏离子通道，以及易患室上和室性心律失常的机制，包括激素信号和自主神经系统，以及如何理解它们的功能相互作用可能有助于开发和优化有效的临床和治疗干预措施，并对时间疗法产生影响。
Circadian rhythms are involved in many physiological and pathological processes in different tissues, including the heart. Circadian rhythms play a critical role in adverse cardiac function with implications for heart failure and sudden cardiac death, highlighting a significant contribution of circadian mechanisms to normal sinus rhythm in health and disease. Cardiac arrhythmias are a leading cause of morbidity and mortality in patients with heart failure and likely cause ∼250,000 deaths annually in the United States alone; however, the molecular mechanisms are poorly understood. This suggests the need to improve our current understanding of the underlying molecular mechanisms that increase vulnerability to arrhythmias. Obesity and its associated pathologies, including diabetes, have emerged as dangerous disease conditions that predispose to adverse cardiac electrical remodeling leading to fatal arrhythmias. The increasing epidemic of obesity and diabetes suggests vulnerability to arrhythmias will remain high in patients. An important objective would be to identify novel and unappreciated cellular mechanisms or signaling pathways that modulate obesity and/or diabetes. In this review we discuss circadian rhythms control of metabolic and environmental cues, cardiac ion channels, and mechanisms that predispose to supraventricular and ventricular arrhythmias including hormonal signaling and the autonomic nervous system, and how understanding their functional interplay may help to inform the development and optimization of effective clinical and therapeutic interventions with implications for chronotherapy.
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