Circadian Governance of Cardiac Growth.
Circadian Governance of Cardiac Growth.
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DOI：
10.3390/cells11091494
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发表时间：
2022-04-29
期刊：
影响因子：
6
通讯作者：
Young, Martin E.
中科院分区：
文献类型：
--
作者：
Latimer, Mary N.;Young, Martin E.
心肌细胞的生物钟在时间上控制着基本的细胞过程，导致心脏特性(如电生理和收缩能力)的24小时节律。有报道称，这一机制的破坏会导致不利的心脏重构和心力衰竭，这突显了这种细胞自主时钟的重要性。在健康的非应激小鼠中，心肌细胞昼夜节律时钟在从清醒到睡眠的转变(相对于清醒时期中期的最低值)适度增加心脏蛋白质合成(~14%)和质量(~11%)。然而，在从清醒到睡眠的转变中，心脏生长能力的增加加剧了心脏对促肥大刺激/应激(例如，肾上腺素能刺激、营养物质)的反应性。心肌细胞的昼夜节律时钟通过许多机制来协调心脏生长过程中依赖时间的节律。核糖体RNA(如28S)和PI3K/AKT/mTOR/S6信号轴都受昼夜节律调节，在心脏从清醒到睡眠的转变中达到顶峰。相反，翻译的负调控因子(包括PER2、AMPK和综合应激反应)在清醒中期协同升高。我们推测，在非低血压/夜间高血压、睡眠呼吸暂停和/或倒班工作期间，持续的心脏生长昼夜节律控制可能会加剧左室肥厚和心脏病的发展，这突显了推进时间治疗干预的必要性。
The cardiomyocyte circadian clock temporally governs fundamental cellular processes, leading to 24-h rhythms in cardiac properties (such as electrophysiology and contractility). The importance of this cell-autonomous clock is underscored by reports that the disruption of the mechanism leads to adverse cardiac remodeling and heart failure. In healthy non-stressed mice, the cardiomyocyte circadian clock modestly augments both cardiac protein synthesis (~14%) and mass (~11%) at the awake-to-sleep transition (relative to their lowest values in the middle of the awake period). However, the increased capacity for cardiac growth at the awake-to-sleep transition exacerbates the responsiveness of the heart to pro-hypertrophic stimuli/stresses (e.g., adrenergic stimulation, nutrients) at this time. The cardiomyocyte circadian clock orchestrates time-of-day-dependent rhythms in cardiac growth through numerous mechanisms. Both ribosomal RNA (e.g., 28S) and the PI3K/AKT/mTOR/S6 signaling axis are circadian regulated, peaking at the awake-to-sleep transition in the heart. Conversely, the negative regulators of translation (including PER2, AMPK, and the integrated stress response) are elevated in the middle of the awake period in a coordinated fashion. We speculate that persistent circadian governance of cardiac growth during non-dipping/nocturnal hypertension, sleep apnea, and/or shift work may exacerbate left ventricular hypertrophy and cardiac disease development, highlighting a need for the advancement of chronotherapeutic interventions.
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影响因子：
2.9
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