Year: 2008
Type: dissertation
Abstract: 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.The clinical incidence of several cardiovascular events, such as myocardial infarction, and stroke has been reported to exhibit circadian variations, with the highest frequency in the morning (4, 11, 26) Although the mechanisms underlying this variation remain unclear, considerable evidence indicates a role of the endogenous fibrinolytic system: circadian variations in the levels of plasminogen activator inhibitor-1 (PAI-1)-a key regulator of fibrinolysis-have been recognized (2, 18).In mammals, circadian rhythms are generated by transcriptional-translational feedback loops orchestrated by a set of clock genes (1,6,7).The heterodimer of CLOCK and brain and muscle arnt-like protein (BMAL) binds to the E-box sites upstream of period and cryptochrome genes and transactivates these genes.The transactivation of the PER and CRY
Author: Masuda, Yoko
Institution: Kobe University
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7145369031