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Journal of Biological Rhythms
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Circadian Rhythms in Mouse Blood Coagulation

Cristiano Bertolucci

Department of Biology and Neuroscience Centre, University of Ferrara, Ferrara, Italy, bru{at}unife.it

Mirko Pinotti

Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy

Ilaria Colognesi

Department of Biology and Neuroscience Centre, University of Ferrara, Ferrara, Italy

Augusto Foà

Department of Biology and Neuroscience Centre, University of Ferrara, Ferrara, Italy

Francesco Bernardi

Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy

Francesco Portaluppi

Hypertension Center, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy

The circadian clock, influencing many biological processes, has been demonstrated to modulate levels of specific coagulation factors, but its impact on the coagulation efficiency is unknown. In a mouse model, the authors evaluated the temporal variations in the initial rate of activated factor X (FXa) and thrombin generation. Upon coagulation activation through the FVIIa-TF pathway (extrinsic activation), both parameters showed rhythmic variations with a significant peak at ZT 12, the light-to-dark transition. In mice subjected to a 6-h delayed light-dark cycle, the peak was shifted as expected. These cyclic oscillations were also observed in constant darkness, thus demonstrating, for the first time, the existence of strong circadian rhythms of the initial rate of either FXa or thrombin generation activity levels. These circadian variations overlapped with those that have been recently described in factor VII (FVII) activity. The peak of FXa generation activity was simulated by the addition of purified human FVII, thus indicating that circadian variations in FVII activity are important determinants of the circadian rhythm of the procoagulant cascade efficiency. These findings help to elucidate the complex control on the coagulation process and might contribute in explaining the temporal variations in the frequency of cardiovascular events observed in humans.

Key Words: circadian rhythms • clocks • blood coagulation • factor Xa generation • thrombin generation

Journal of Biological Rhythms, Vol. 20, No. 3, 219-224 (2005)
DOI: 10.1177/0748730405275654
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