title: Daily and circadian rhythms of tissue factor pathway inhibitor and factor VII activity.
abstract: 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.
authors.affiliation: Deparment of di Biochimica e Biologia Molecolare, Università di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italia. pnm@unife.it
authors.forename: Mirko
authors.initials: M
authors.lastname: Pinotti
authors.forename: Cristiano
authors.initials: C
authors.lastname: Bertolucci
authors.forename: Francesco
authors.initials: F
authors.lastname: Portaluppi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Colognesi
authors.forename: Elena
authors.initials: E
authors.lastname: Frigato
authors.forename: Augusto
authors.initials: A
authors.lastname: Foà
authors.forename: Francesco
authors.initials: F
authors.lastname: Bernardi
mesh_terms: 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*
chemical_list: D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII