Daily and circadian rhythms of tissue factor pathway inhibitor and factor VII activity.
OBJECTIVE
Diurnal variations in levels of factor VII (FVII), FVIII, proteins C and S, antithrombin, plasminogen activator inhibitor-1, prothrombin fragment F1+2, and D-dimers in healthy humans point to the existence of circadian rhythms of coagulation factors. We sought for temporal fluctuations of tissue factor pathway inhibitor (TFPI) activity in human and mouse plasma.


RESULTS
TFPI activity showed significant daily variations with highest levels in the morning in healthy men (+11%) and in mice at the light-to-dark transition (+63%), the beginning of the physically active period. Variations in FVII activity paralleled those in TFPI. In mice, the feeding schedule had a strong impact on these rhythms. Although restricted feeding and fasting shifted the peak of TFPI, the FVII peak disappeared. Investigation of temporal fluctuations in constant darkness indicated the existence of daily rhythms for TFPI and of true circadian rhythms for FVII.


CONCLUSIONS
For the first time, we report, both in humans and mice, temporal variations in TFPI activity. The coherent variations in FVII and TFPI activity could interplay to maintain the coagulation equilibrium. The chronobiological patterns should be considered to analyze activity levels of these factors. Moreover, the mouse model could be exploited to investigate modifiers of coagulation rhythms potentially associated to morning peaks of cardiovascular events.
Pinotti
Mirko
M
Deparment of di Biochimica e Biologia Molecolare, Università di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italia. pnm@unife.it
Bertolucci
Cristiano
C
Portaluppi
Francesco
F
Colognesi
Ilaria
I
Frigato
Elena
E
Foà
Augusto
A
Bernardi
Francesco
F
D000328:Adult; D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D004435:Eating; D005167:Factor VII / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013927:Thrombosis / Q000097:blood / Q000503:physiopathology*
D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII