title: Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle.
abstract: Serious adverse cardiovascular events peak in the morning, possibly related to increased thrombosis in critical vessels. Plasminogen activator inhibitor-1 (PAI-1), which inhibits fibrinolysis, is a key circulating prothrombotic factor that rises in the morning in humans. We tested whether this morning peak in PAI-1 is caused by the internal circadian system or by behaviors that typically occur in the morning, such as altered posture and physical activity. Twelve healthy adults underwent a 2-week protocol that enabled the distinction of endogenous circadian effects from behavioral and environmental effects. The results demonstrated a robust circadian rhythm in circulating PAI-1 with a peak corresponding to ∼6:30 am. This rhythm in PAI-1 was 8-times larger than changes in PAI-1 induced by standardized behavioral stressors, including head-up tilt and 15-minute cycle exercise. If this large endogenous morning peak in PAI-1 persists in vulnerable individuals, it could help explain the morning peak in adverse cardiovascular events.
authors.affiliation: Medical Chronobiology Program, Division of Sleep Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA; and.
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.forename: Steven A
authors.initials: SA
authors.lastname: Shea
mesh_terms: D000328:Adult; D001519:Behavior; D001777:Blood Coagulation; D002940:Circadian Rhythm; D015444:Exercise; D005260:Female; D005342:Fibrinolysis; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012307:Risk Factors; D012890:Sleep; D013696:Temperature; D013997:Time Factors; D014851:Wakefulness; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1