Summary
The mechanism underlying diurnal variations in PAI-1 as well as the cellular origin
of PAI-1 in subjects with high PAI-1 levels are unknown. We evaluated diurnal changes
(8:00 am vs 4:00 pm) in PAI-1 (functional and immunological assays), t-PA Ag and t-PA/PAI-1
complex levels in controls and subjects with high PAI-1 levels. Three test groups
were recruited among obese hyperinsulinmic subjects, emergency care unit patients
with inflammatory syndrome or infection and pregnant women.
The classical afternoon decrease of PAI-1 level was observed in controls and obese
subjects but its amplitude was greater in the latter. The decrease in t-PA Ag and
t-PA/PAI-1 complex levels was the same in controls and in obese. As, in previous studies,
elevated PAI-1 levels have been correlated with insulin resistance and a decrease
in insulin sensibility has been described in the early morning, it is proposed that
this “dawn phenomenon” could be implicated in the circadian variations of PAI-1 in
controls and could be amplified in obese subjects. Great variability in PAI-1, t-PA
Ag or t-PA/PAI-1 complex levels was observed in patients with acute inflammatory syndrome
or infection for whom classical biorhythms are suppressed. No diurnal changes in PAI-1
and other fibrinolytic parameters were observed in patients with inflammatory syndrome
or in pregnant women suggesting that other sources and/or other regulatory mechanisms
of PAI-1 production are involved.