AbstractThe circadian clock is an evolutionarily conserved time-keeper that regulates physiological processes across 24 h. In the cardiovascular system, several parameters, such as blood pressure, heart rate, and metabolism, exhibit time-of-day variations. These features are in part driven by the circadian clock.

摘要生物钟是一种进化上保守的时间保持器，可调节24小时的生理过程。在心血管系统中，血压，心率和新陈代谢等几个参数表现出一天中的时间变化。这些特征部分是由生物钟驱动的。

Chronic perturbation of diurnal rhythmicity due to shift work or irregular social schedules has been associated with an increased risk of hypertension, arrhythmias, and myocardial infarction. This review discusses the impact of circadian rhythms on human cardiovascular health and the effect of clock disruption on the occurrence of adverse cardiac events.

由于轮班工作或不规则的社交时间表导致的昼夜节律的慢性紊乱与高血压，心律不齐和心肌梗塞的风险增加有关。本综述讨论了昼夜节律对人类心血管健康的影响以及时钟中断对不良心脏事件发生的影响。

Additionally, we discuss how the main risk factors of cardiovascular diseases, such as obesity, sleep disorders, and aging, affect circadian rhythms. Finally, we elaborate on chronotherapy as well as on targeting the clock and highlight novel approaches to translate our scientific understanding of the circadian clock into clinical practice..

此外，我们还讨论了肥胖，睡眠障碍和衰老等心血管疾病的主要危险因素如何影响昼夜节律。最后，我们详细介绍了时间疗法以及针对时钟的方法，并强调了将我们对生物钟的科学理解转化为临床实践的新方法。。

IntroductionNearly all forms of life on our planet organize physiological and behavioral processes in an oscillatory fashion within a 24-h cycle. This motion is entrained by the rotation of the earth and the resulting light-dark cycles1,2. Together with other external cues, such as food intake or exercise, these so-called Zeitgebers (time-givers) allow for anticipation of daily changes in the environment.

。这种运动受到地球自转和由此产生的明暗循环的夹带1,2。这些所谓的时代赋予者（time givers）与其他外部线索（如食物摄入或锻炼）一起，可以预测环境的日常变化。

This is achieved by translating these cues into oscillations and synchronization of internal processes. For instance, higher body temperature and glucose metabolism are associated with greater energetic needs during the wake time of an organism3,4. A gene-regulatory network of transcription factors, called core clock factors, underlies circadian rhythmicity5.

这是通过将这些线索转化为内部过程的振荡和同步来实现的。例如，较高的体温和葡萄糖代谢与生物体觉醒期间更大的能量需求相关3,4。转录因子的基因调控网络，称为核心时钟因子，是昼夜节律的基础5。

Clock factors regulate clock-controlled genes (CCGs) that, as a result, are expressed in an oscillatory manner. The central or master clock is located in the suprachiasmatic nucleus of the hypothalamus and acts as a central pacemaker that is entrained mainly by light and controls sleep-wake cycles through the secretion of hormones, such as melatonin6.

。中央或主时钟位于下丘脑的视交叉上核，起着中枢起搏器的作用，主要由光线夹带，并通过分泌激素（如褪黑激素6）来控制睡眠-觉醒周期。

Via neural and humoral signals, the central clock relays this information to peripheral organs, thereby synchronizing this information. Peripheral clocks control circadian homeostasis and are present at all organizational levels of the body, including in cells, tissues, and organs5,7. Peripheral clocks can also be entrained directly by Zeitgebers, such as food and exercise.In the cardiovascular system, several physiological parameters exhibit time-of-day variations.

中央时钟通过神经和体液信号将这些信息传递给外周器官，从而使这些信息同步。外围时钟控制昼夜节律稳态，并存在于身体的所有组织水平，包括细胞，组织和器官5,7。外围时钟也可能直接受到时代的影响，例如食物和运动。在心血管系统中，一些生理参数表现出一天中的时间变化。

For instance, blood pressure (BP)8, heart rate (HR)9, vascular tone10, and myocardial metabolism11 are regulated in a circadian manner. Importantly, their rhythmicity is essential for proper cardiac funct.

例如，血压（BP）8，心率（HR）9，血管张力10和心肌代谢11以昼夜节律方式调节。重要的是，它们的节律性对于正确的心脏功能至关重要。

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Download referencesAcknowledgementsThis work was funded by the Deutsches Zentrum für Herz-Kreislauf-Forschung e.V. (DZHK) and the Cardiopulmonary Institute (CPI). We kindly thank Margo Favier for help with the figures, Bryce J. Carpenter for proofreading, and Marit W. Vermunt for extensive editing of the manuscript.Author informationAuthor notesThese authors contributed equally: Margaux Lecacheur, Daniëlle J.

下载参考文献致谢这项工作由Deutsches Zentrum für Herz Kreislauf Forschung e.V.（DZHK）和心肺研究所（CPI）资助。我们衷心感谢Margo Favier对数字的帮助，Bryce J.Carpenter的校对，以及Marit W.Vermunt对手稿的广泛编辑。作者信息作者注意到这些作者做出了同样的贡献：Margaux Lecacheur，Daniëlle J。

M. Ammerlaan.Authors and AffiliationsMax Planck Institute for Heart and Lung Research, Bad Nauheim, GermanyMargaux Lecacheur, Daniëlle J. M. Ammerlaan & Pieterjan DierickxCardiopulmonary Institute (CPI), Bad Nauheim, GermanyMargaux Lecacheur & Pieterjan DierickxGerman Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Bad Nauheim, GermanyMargaux Lecacheur & Pieterjan DierickxAuthorsMargaux LecacheurView author publicationsYou can also search for this author in.

M、 。作者和附属机构马克斯·普朗克心肺研究所，巴德瑙海姆，德国玛歌·勒卡丘，丹尼尔·J·M·阿默兰和皮埃特扬·迪瑞克心脏肺研究所（CPI），巴德瑙海姆，德国玛歌·勒卡丘和皮埃特扬·迪瑞克德国心血管研究中心（DZHK），合作网站莱茵河，巴德瑙海姆，德国玛歌·勒卡丘和皮埃特扬·迪瑞克作者MARGAUX LecacheurView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarDaniëlle J. M. AmmerlaanView author publicationsYou can also search for this author in

PubMed Google ScholarDaniëlle J.M.AmmerlaanView作者出版物您也可以在

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PubMed Google ScholarContributionsM.L. and D.J.M. wrote the initial draft of the manuscript. D.J.M. and P.D. prepared the figures. P.D. conceived and revised the manuscript. All authors approved the final version of the manuscript.Corresponding authorCorrespondence to

PubMed谷歌学术贡献。五十、 D.J.M.撰写了手稿的初稿。D、 J.M.和P.D.准备了这些数字。P、 D.构思并修改了手稿。所有作者都批准了稿件的最终版本。对应作者对应

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Reprints and permissionsAbout this articleCite this articleLecacheur, M., Ammerlaan, D.J.M. & Dierickx, P. Circadian rhythms in cardiovascular (dys)function: approaches for future therapeutics.

转载和许可本文引用本文Lecacheur，M.，Ammerlaan，D.J.M。＆Dierickx，P。心血管（dys）功能的昼夜节律：未来治疗方法。

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