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2003 Fiscal Year Final Research Report Summary

Molecular mechanisms of circadian oscillation of cardiovascular function regulated by the internal biological clock

Research Project

Project/Area Number 14370220
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

MAEMURA Koji  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (90282649)

Co-Investigator(Kenkyū-buntansha) HAYASHI Dobun  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (80313104)
NAGAI Ryozo  The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (60207975)
Project Period (FY) 2002 – 2003
Keywordscircadian rhythm / biological clock / cardiovascular function / molecular biology / transgenic mouse / myocardial infraction / endothelial cell / microarray
Research Abstract

Human physiological activities are under the control of circadian rhythm, and the internal biological clock is responsible for this rhythmicity. Although increasing evidence has shown the existence of biological clocks in peripheral tissues, the functional relevance of.the peripheral clock still remains to be elucidated. 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 tried to identify the target genes of the peripheral clock. One of the candidate genes we identified was PAT-1. We demonstrated that PAI-1 mRNA levels exhibited circadian variation in mouse peripheral organs. Then, we demonstrated that CLOCK and BMAL increased PAI-1 gene expression … More 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. To further identify the target genes of the peripheral clock in cardiovascular systems, we performed cDNA microarray analysis using RNA from vascular endothelial cells treated with adenoviruses expressing CLOCK and CLIF/BMAL2. One of the genes identified by this method was DEC1, a bHLH transcription factor that was recently reported as a component of the biological clock. Now, we are analyzing other genes we isolated as candidate genes regulated by the peripheral 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. We further generated transgenic mice whose biological clocks are destroyed specifically in vascular endothelial cells. Using these mice, we are about to analyze the role of peripheral clock separately from the central clock. These results potentially provide a molecular basis for the circadian variation of cardiovascular function and novel strategies for the treatment of cardiovascular diseases. Less

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Kawanami D, et al.: "Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells : a new insight into adipocytokine-endothelial cell interactions."Biochem Biophys Res Commun.. 314. 415-419 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawamoto T, et al.: "A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation."Biochem Biophys Res Commun.. 313. 117-124 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamauchi T, et al.: "Cloning of adiponectin receptors that mediate antidiabetic metabolic effects."Nature. 423. 762-769 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maemura K, et al.: "Novel insight into the role of endothelial PAS domain protein 1 in congestive heart failure."J Mol Cell Cardiol.. 34. 703-707 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shindo T, et al.: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling."Nat Med.. 8. 856-863 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawanami D, et al.: "Direct reciprocal effects of resistin and adiponectin on vascular.endothelial cells : a new insight into adipocytokine-endothelial cell interactions."Biochem Biophys Res Commun.. 314. 415-419 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawamoto T, et al.: "A novel autofeedback loop of Dec 1 transcription involved in circadian rhythm regulation."Biochem Biophys Res Commun.. 313. 117-124 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamauchi T, et al.: "Cloning of adiponectin receptors that mediate antidiabetic metabolic effects."Nature. 423. 762-769 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maemura K, et al.: "Novel insight into the role of endothelial PAS domain protein l in congestive heart failure."J Mol Cell Cardiol.. 34. 703-707 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shindo T, et al.: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling."Nat Med.. 8. 856-863 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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