Abstract
To elucidate which component(s) of thei fibrinolytic system is (are) responsible for
the diurnal variation of fibrinolytic activity we have studied several parameters
of this system in 8 healthy male volunteers during a period of. 24 h. Blood was collected
at 8 a. m., 10 a. m., 12 a. m., 4 p.m., 8 p.m. and 8 a. m. next morning. The following
tests were performed: euglobulin clot lysis time (ECLT), fibrinolytic activity of
euglobulins on fibrin plates in the presence and absence of blocking antibodies to
tissue-type plasminogen activator (t-PA) and/or urokinase (u-PA), overall plasminogen
activator inhibitor (PAI) activity, antigen levels of t-PA, u-PA and PAI-I and zymography
of the euglobulin fraction after SDS-PAGE. From 8-10 a. m. to 4-8 p. m., total fibrinolytic
activity increased by 1l3% (p <0.01) or 71%h (p <0.01) when measured by ECIX or by
fibrin plate assay, respectively. The immunoquenching experiments showed that this
increase was entirely due to t-PA related activity whereas u-PA activity and t-PA/u-PA
independent activity remained constant during the day. Average antigen levels of u-PA
and t-PA in the afternoon were 6% and 25% lower than those measured in the morning.
During this period, overall PAI activity and PAI-1 antigen decreased by 3l% (p <0.01)
and 52% (p <0.01) respectively. Electrophoretic-zymographic analysis of_ the euglobulins
revealed that throughout the day the majority of t-PA was present in the form of the
110 kDa t-PA/PAI-I complex. The intensity of this cornplex was lowest in the afternoon.
Free t-PA was almost undetectable in morning samples, but constituted a significant
proportion of total t-PA in the afternoon. The diurnal increase of fibrinolytic activity,
therefore, is not due to an augmentation of antigen levels of t-PA and/or u-PA but
to a decline of those of PAI-1.
Keywords
Diurnal - Fibrinolytic activity - PAI activity - t-PA - u-PA - PAI-1
