Takeda Norihiko, Maemura Koji
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan,
Cell Mol Life Sci. 2015 Sep;72(17):3225-34. doi: 10.1007/s00018-015-1923-1. Epub 2015 May 14.
The time of onset of cardiovascular disorders such as myocardial infarctions or ventricular arrhythmias exhibits a circadian rhythm. Diurnal variations in autonomic nervous activity, plasma cortisol level or renin-angiotensin activity underlie the pathogenesis of cardiovascular diseases. Transcriptional-translational feedback loop of the clock genes constitute a molecular clock system. In addition to the central clock in the suprachiasmatic nucleus, clock genes are also expressed in a circadian fashion in each organ to make up the peripheral clock. The peripheral clock seems to be beneficial for anticipating external stimuli and thus contributes to the maintenance of organ homeostasis. Loss of synchronization between the central and peripheral clocks also augments disease progression. Moreover, accumulating evidence shows that clock genes affect inflammatory and intracellular metabolic signaling. Elucidating the roles of the molecular clock in cardiovascular pathology through the identification of clock controlled genes will help to establish a novel therapeutic approach for cardiovascular disorders.
心肌梗死或室性心律失常等心血管疾病的发病时间呈现昼夜节律。自主神经活动、血浆皮质醇水平或肾素 - 血管紧张素活性的昼夜变化是心血管疾病发病机制的基础。时钟基因的转录 - 翻译反馈环构成了分子时钟系统。除了视交叉上核中的中央时钟外，时钟基因也以昼夜节律的方式在每个器官中表达，从而构成外周时钟。外周时钟似乎有利于预测外部刺激，因此有助于维持器官内环境稳定。中央和外周时钟之间同步性的丧失也会加速疾病进展。此外，越来越多的证据表明，时钟基因会影响炎症和细胞内代谢信号传导。通过识别时钟控制基因来阐明分子时钟在心血管病理学中的作用，将有助于建立一种针对心血管疾病的新型治疗方法。
