Molecular mechanisms of morning onset of myocardial infarction.
Ann N Y Acad Sci
; 947: 398-402, 2001 Dec.
Article
em En
| MEDLINE
| ID: mdl-11795300
ABSTRACT
We recently isolated a novel bHLH/PAS protein, CLIF (cycle like factor), by yeast two-hybrid screening of human umbilical endothelial cell cDNA library. CLIF is preferentially expressed in endothelial and neuronal cells. Because CLIF is expressed in vascular endothelial cells and forms a heterodimer with CLOCK, the key transcription factor controlling the circadian rhythm, we hypothesized that CLIF regulates the circadian oscillation of PAI-1 gene expression in endothelial cells. Northern blot analysis of mouse organs showed circadian oscillations of PAI-I mRNA levels. In addition, the clock-related genes also showed circadian oscillation in peripheral tissues. In endothelial cells, the heterodimer of CLIF and CLOCK upregulated the PAI-1 gene expression through E-box sites. Furthermore, Period and Cryptochrome, which are negative regulators in the feedback loop of the biological clock, inhibited PAI-1 promoter activation by the CLOCKCLIF heterodimer. These results suggest that the peripheral tissues have their own biological clock and CLIF regulates the circadian oscillation of PAI-1 gene expression in endothelial cells. This study suggests a novel molecular mechanism of the morning onset of myocardial infarction. Here we review our recent work and literature.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ritmo Circadiano
/
Infarto do Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Ann N Y Acad Sci
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Japão