The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors

Frank A J L Scheer, Alan D. Michelson, Andrew L. Frelinger, Heather Evoniuk, Erin E. Kelly, Mary McCarthy, Lauren A. Doamekpor, Marc R. Barnard, Steven Shea

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.

Original languageEnglish (US)
Article numbere24549
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 8 2011
Externally publishedYes

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platelet activation
Platelet Activation
Platelets
circadian rhythm
Blood Platelets
Chemical activation
sleep
blood platelet count
platelet aggregation
myocardial infarction
thrombosis
epinephrine
stroke
epidemiological studies
body temperature
Circadian Rhythm
glycoproteins
exercise
Sleep
Platelet Membrane Glycoproteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors. / Scheer, Frank A J L; Michelson, Alan D.; Frelinger, Andrew L.; Evoniuk, Heather; Kelly, Erin E.; McCarthy, Mary; Doamekpor, Lauren A.; Barnard, Marc R.; Shea, Steven.

In: PLoS One, Vol. 6, No. 9, e24549, 08.09.2011.

Research output: Contribution to journalArticle

Scheer, FAJL, Michelson, AD, Frelinger, AL, Evoniuk, H, Kelly, EE, McCarthy, M, Doamekpor, LA, Barnard, MR & Shea, S 2011, 'The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors', PLoS One, vol. 6, no. 9, e24549. https://doi.org/10.1371/journal.pone.0024549
Scheer, Frank A J L ; Michelson, Alan D. ; Frelinger, Andrew L. ; Evoniuk, Heather ; Kelly, Erin E. ; McCarthy, Mary ; Doamekpor, Lauren A. ; Barnard, Marc R. ; Shea, Steven. / The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors. In: PLoS One. 2011 ; Vol. 6, No. 9.
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abstract = "Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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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