Daytime Fluctuations of Plasminogen Activator Inhibitor 1 (PAI-1) in Populations with High PAI-1 Levels

Abstract

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 hyperinsulinemic 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.