Chen Yung-Lung, Lin Pei-Ting, Yang Ming-Yu, Chuang Jiin-Haur
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Int J Cardiol. 2025 Oct 15;437:133463. doi: 10.1016/j.ijcard.2025.133463. Epub 2025 Jun 9.
The light-dark (LD) cycle regulates circadian rhythms that influence cardiac function and autonomic regulation. However, the impact of LD cycle disturbances on cardiac electrophysiology and gene expression remains unclear. This study investigated how disrupted light exposure affects cardiac rhythm, function, and gene expression in mice.
Eight-week-old C57BL/6 J mice were exposed to either a normal LD cycle (12 h light/12 h dark, NLD) or a disrupted LD cycle (24 h light for 3 days/24 h dark for 4 days, DLD) for 12 and 24 weeks. Monthly electrocardiographic (ECG) and echocardiographic assessments were performed. Gene expression related to circadian regulation, mitochondrial function, and cardiac remodeling was analyzed.
DLD mice exhibited transient weight gain and persistent cardiac hypertrophy. ECG analysis showed shortened RR intervals, prolonged QTc intervals (weeks 4 and 8), and widened QRS duration (week 16). Heart rate variability analysis indicated sustained sympathovagal imbalance (increased LF/HF ratio). Echocardiography revealed early cardiac remodeling with increased left ventricular outflow tract velocity, pressure gradient, and internal diameter. Gene analysis showed early Per2 and Nr1d1 dysregulation, followed by Bmal1, Clock, Rora, and Rorc downregulation and Nr1d1 upregulation at 24 weeks. Mitochondrial dysfunction, fibrosis, and inflammation markers were also dysregulated.
Chronic LD disruption leads to circadian misalignment, autonomic imbalance, and cardiac remodeling, potentially contributing to adverse cardiovascular outcomes.
This model simulates circadian disruption in shift workers and individuals with irregular sleep patterns, highlighting prolonged circadian misalignment may elevate cardiovascular risk and the importance of circadian health in cardiovascular prevention strategies.
明暗（LD）循环调节昼夜节律，昼夜节律会影响心脏功能和自主神经调节。然而，LD循环紊乱对心脏电生理和基因表达的影响仍不清楚。本研究调查了光照中断如何影响小鼠的心律、功能和基因表达。
将8周龄的C57BL/6 J小鼠暴露于正常的LD循环（12小时光照/12小时黑暗，NLD）或打乱的LD循环（3天24小时光照/4天24小时黑暗，DLD）中，持续12周和24周。每月进行心电图（ECG）和超声心动图评估。分析与昼夜调节、线粒体功能和心脏重塑相关的基因表达。
DLD小鼠出现短暂体重增加和持续性心脏肥大。心电图分析显示RR间期缩短、QTc间期延长（第4周和第8周）以及QRS波时限增宽（第16周）。心率变异性分析表明存在持续的交感迷走神经失衡（LF/HF比值增加）。超声心动图显示早期心脏重塑，左心室流出道速度、压力梯度和内径增加。基因分析显示，早期Per2和Nr1d1失调，随后在24周时Bmal1、Clock、Rora和Rorc下调，Nr1d1上调。线粒体功能障碍、纤维化和炎症标志物也失调。
长期的LD紊乱会导致昼夜节律失调、自主神经失衡和心脏重塑，可能导致不良心血管结局。
该模型模拟了轮班工作者和睡眠模式不规律个体的昼夜节律紊乱，强调了长期的昼夜节律失调可能会增加心血管风险，以及昼夜节律健康在心血管预防策略中的重要性。
