The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.
The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.
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DOI：
10.1371/journal.pone.0024549
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shea SA
中科院分区：
文献类型：
--
作者：
Scheer FA;Michelson AD;Frelinger AL 3rd;Evoniuk H;Kelly EE;McCarthy M;Doamekpor LA;Barnard MR;Shea SA
血小板参与血栓形成，是心肌梗死和缺血性中风的核心。这些不良心血管事件具有昼夜模式，在早上（上午9点）达到峰值，可能与血小板激活的内源性生物钟控制有关。目的是测试人类内源性昼夜节律系统是否影响(1)血小板功能和(2)血小板对标准化行为应激源的反应。我们还旨在比较昼夜节律系统对血小板功能的影响程度与各种标准化行为应激源（包括心算、被动姿势倾斜和轻度骑车运动）对血小板功能的影响程度。我们研究了12名健康成年人（6名女性），他们在单独的实验室套房中在昏暗的光线下生活了240小时，所有的行为都被安排在20小时的循环周期中，以便评估内源性昼夜节律功能，而不受环境和行为的影响，包括睡眠/觉醒周期。根据核心体温评估昼夜节律。血小板表面活化糖蛋白（GP） IIb-IIIa、GPIb和p -选择素具有高度显著的内源性昼夜节律（峰谷振幅为6-17%，p≤0.01）。这些昼夜节律高峰发生在与上午8 - 9点相对应的昼夜节律阶段。血小板计数、ATP释放、聚集性和血浆肾上腺素也有明显的昼夜节律，但峰值较晚（对应于下午3 - 8点）。对血小板激活标志物的昼夜节律影响总是大于任何三种行为应激源。这些数据证明了内源性昼夜节律系统对人类血小板激活的强大影响——不受睡眠/觉醒周期、其他行为影响和环境的影响。三种血小板表面标记物（包括血小板表面活化的GPIIb-IIIa，血小板聚集的最终共同途径）的昼夜节律高峰时间为上午9点，这表明内源性昼夜节律对血小板功能的影响可能导致许多流行病学研究中发现的不良心血管事件的早晨高峰。
Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (∼9AM), potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise. We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6–17% peak-trough amplitudes; p≤0.01). These circadian peaks occurred at a circadian phase corresponding to 8–9AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3–8PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors. These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans—independent of the sleep/wake cycle, other behavioral influences and the environment. The ∼9AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian influences on platelet function could contribute to the morning peak in adverse cardiovascular events as seen in many epidemiological studies.
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DOI：
10.1073/pnas.0808180106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Scheer, Frank A. J. L.;Hilton, Michael F.;Shea, Steven A.
通讯作者：
Shea, Steven A.
影响因子：
37.8
作者：
KESTIN, AS;ELLIS, PA;MICHELSON, AD
通讯作者：
MICHELSON, AD
影响因子：
158.5
作者：
MULLER, JE;STONE, PH;BRAUNWALD, E
通讯作者：
BRAUNWALD, E
影响因子：
20.3
作者：
LIBRE, EP;COWAN, DH;SHULMAN, NR
通讯作者：
SHULMAN, NR
影响因子：
--
作者：
RODEN, M;KOLLER, M;WALDHAUSER, F
通讯作者：
WALDHAUSER, F