Plasminogen Activator Inhibitor-1 and the Circadian Clock in Metabolic Disorders

Plasma PAI-1 levels robustly fluctuate in a circadian manner and consequently contribute to hypofibrinolysis during the early morning. The circadian expression of PAI-1 gene is thought to be directly regulated by the circadian clock proteins such as CLOCK and BMAL1/BMAL2 which drive the endogenous biological clock. Plasma PAI-1 levels are increased in the beginning of the active phase in both diurnal humans and in nocturnal rodents, suggesting that the rhythmic PAI-1 expression is commonly indispensable for organisms. A series of our recent studies revealed that circadian clock proteins are important for hypofibrinolysis induced by metabolic disorders such as obesity and diabetes.