Reilly Dermot F, Westgate Elizabeth J, FitzGerald Garret A
Institute for Translational Medicine and Therapeutics, 153 Johnson Pavilion, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1694-705. doi: 10.1161/ATVBAHA.107.144923. Epub 2007 May 31.
Living organisms have adapted to the daily rotation of the earth and regular changes in the light environment. Life forms anticipate environmental transitions, adapt their own physiology, and perform activities at behaviorally advantageous times during the day. This is achieved by means of endogenous circadian clocks that can be synchronized to the daily changes in external cues, most notably light and temperature. For many years it was thought that neurons of the suprachiasmatic nucleus (SCN) uniquely controlled circadian rhythmicity of peripheral tissues via neural and humoral signals. The cloning and characterization of mammalian clock genes revealed that they are expressed in a circadian manner throughout the body. It is now accepted that peripheral cells, including those of the cardiovascular system, contain a circadian clock similar to that in the SCN. Many aspects of cardiovascular physiology are subject to diurnal variation, and serious adverse cardiovascular events including myocardial infarction, sudden cardiac death, and stroke occur with a frequency conditioned by time of day. This has raised the possibility that biological responses under the control of the molecular clock might interact with environmental cues to influence the phenotype of human cardiovascular disease.
生物已经适应了地球的每日自转以及光照环境的规律性变化。生命形式能够预测环境转变,调整自身生理机能,并在一天中行为上有利的时间进行活动。这是通过内源性生物钟实现的,生物钟可以与外部线索(最显著的是光照和温度)的每日变化同步。多年来,人们一直认为视交叉上核(SCN)的神经元通过神经和体液信号独特地控制着外周组织的昼夜节律。哺乳动物生物钟基因的克隆和特性分析表明,它们在全身以昼夜节律的方式表达。现在人们已经认识到,包括心血管系统细胞在内的外周细胞含有与SCN中类似的生物钟。心血管生理学的许多方面都存在昼夜变化,包括心肌梗死、心源性猝死和中风在内的严重不良心血管事件的发生频率受一天中时间的制约。这就增加了一种可能性,即分子生物钟控制下的生物反应可能与环境线索相互作用,从而影响人类心血管疾病的表型。