Identification of the circadian clock-regulated E-box element in the mouse plasminogen activator inhibitor-1 gene.

摘要

Serious adverse cardiovascular events, including myocardial infarction, sudden cardiac death and stroke, have a pronounced circadian rhythmicity that peaks during the morning. The frequency of infarction in the morning is 1.5-3-fold higher than at other times of the day. Levels of blood plasminogen activator inhibitor-1 (PAI-1), the primary physiologic inhibitor of plasminogen activators, peak during the early morning, which might explain the morning onset of myocardial infarctions . Maemura et al. suggested that the circadian oscillation of human PAI-1 gene expression plays an important role in the circadian fluctuation of blood fibrinolytic activity. Assays in vitro have shown that CL0CK/BMAL2 (CLTF) and CL0CK/BMAL1 heterodimers upregulate human PAI-1 gene expression via two canonical E-box (CACGTG) elements located at bp -677 to -672 and at bp -562 to -557 .