Curtis Anne M, Cheng Yan, Kapoor Shiv, Reilly Dermot, Price Tom S, Fitzgerald Garret A
Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, 153 Johnson Pavilion, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3450-5. doi: 10.1073/pnas.0611680104. Epub 2007 Feb 20.
The diurnal variation in the incidence of myocardial infarction and stroke may reflect an influence of the molecular clock and/or the time dependence of exposure to environmental stress. The circadian variation in blood pressure and heart rate is disrupted in mice, Bmal1(-/-), Clock(mut), and Npas2(mut), in which core clock genes are deleted or mutated. Although Bmal1 deletion abolishes the 24-h frequency in cardiovascular rhythms, a shorter ultradian rhythm remains. Sympathoadrenal function is disrupted in these mice, which reflects control of enzymes relevant to both synthesis (phenylethanolamine N-methyl transferase) and disposition (monoamine oxidase B and catechol-O-methyl transferase) of catecholamines by the clock. Both timing and disruption or mutation of clock genes modulate the magnitude of both the sympathoadrenal and pressor but not the adrenocortical response to stress. Despite diurnal variation of catecholamines and corticosteroids, they are regulated differentially by the molecular clock. Furthermore, the clock may influence the time-dependent incidence of cardiovascular events by controlling the integration of selective asynchronous stress responses with an underlying circadian rhythm in cardiovascular function.
心肌梗死和中风发病率的昼夜变化可能反映了分子时钟的影响和/或暴露于环境应激的时间依赖性。在缺失或突变核心时钟基因的小鼠（Bmal1(-/-)、Clock(mut)和Npas2(mut)）中，血压和心率的昼夜变化受到破坏。虽然Bmal1基因缺失消除了心血管节律的24小时频率，但仍保留较短的超日节律。这些小鼠的交感肾上腺功能受到破坏，这反映了时钟对与儿茶酚胺合成（苯乙醇胺N-甲基转移酶）和代谢（单胺氧化酶B和儿茶酚-O-甲基转移酶）相关酶的控制。时钟基因的时间以及破坏或突变调节了交感肾上腺和升压反应的幅度，但不影响肾上腺皮质对应激的反应。尽管儿茶酚胺和皮质类固醇存在昼夜变化，但它们受分子时钟的调节方式不同。此外，时钟可能通过控制选择性异步应激反应与心血管功能潜在昼夜节律的整合，影响心血管事件的时间依赖性发生率。
