Role of angiotensin and the clock system in the circadian regulation of plasminogen activator inhibitor-1.

The clock system and the renin-angiotensin system (RAS) have been reported to play an important role in the circadian expression of plasminogen activator inhibitor-1 (PAI-1) gene. However, the degree of involvement of these systems remains unknown. In the present study, we investigated the roles of the clock system and the RAS in the circadian expression of PAI-1 in the peripheral tissues in vivo by using Cry1/Cry2 double knockout (Cry1/2-deficient) and angiotensin type 1 (AT1a) receptor knockout (AT1a-deficient) mice. We observed no significant rhythmicity in the PAI-1 expression in all tissues examined in Cry1/2-deficient mice; this suggests that the clock system is indispensable for the circadian expression of PAI-1. In AT1a-deficient mice, apparent circadian oscillation of PAI-1 expression was observed in the lung and liver but not in the kidney, suggesting that AT1a-mediated signaling modulates the circadian expression of PAI-1 in a tissue-specific manner.