Role of Angiotensin and the Clock System in the Circadian Regulation of Plasminogen Activator Inhibitor-1
ABSTRACT The clock system and the renin-angiotensin system (RAS) have been reported toplay 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 thecircadian expression of PAI-1 in the peripheral tissues in vivo by using Cry1/Cry2double knockout (Cry1/2-deficient) and angiotensin type 1 (AT1a) receptor knockout(AT1a-deficient) mice. We observed no significant rhythmicity in the PAI-1 expressionin all tissues examined in Cry1/2-deficient mice; this suggests that the clock system isindispensable for the circadian expression of PAI-1. In AT1a-deficient mice, apparentcircadian oscillation of PAI-1 expression was observed in the lung and liver but not in the kidney, suggesting that AT1a-mediated signaling modulates the circadianexpression of PAI-1 in a tissue-specific manner.