抄録
Cardiovascular function and frequencies of onset of cardiovascular diseases show circadian oscillation. Furthermore, cultured vascular endothelial cells and cardiomyocytes showed circadian oscillation of clock genes expression, suggesting the existence of the peripheral clock in cardiovascular systems. To elucidate the functional relevance of the peripheral clock in cardiovascular system, we first tried to identify the target genes of the peripheral clock. We demonstrated that PAI-1 mRNA levels exhibited circadian variation and that CLOCK and BMAL increased PAI-1gene expression mediated through the E-box sites. The circadian oscillation of PAI-1 gene expression is responsible for the decreased fibrinolytic activity that attributes to the morning onset of myocardial infarction. We further identified several target genes of the peripheral clock by cDNA microarray analysis using RNA from vascular endothelial cells. We are analyzing the function of these genes in cardiovascular system. We next generated transgenic mice in which Cry1, a negative regulator of the molecular clock, is overexpressed specifically in vascular endothelial cells to analyze the function of the peripheral clock separately from the central clock. Taken together, these results suggest that cardiovascular systems have their own peripheral clocks and at least in part, they may regulate the circadian oscillation of cardiovascular function directly. These results potentially provide a molecular basis for the circadian variation of cardiovascular function and novel strategies for the treatment of cardiovascular diseases. [Jpn J Physiol 55 Suppl:S25 (2005)]
