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2001 Fiscal Year Final Research Report Summary

動脈硬化の分子機構

Research Project

Project/Area Number 09281104
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KITA Toru  Kyoto University Professor, 医学研究科, 教授 (60161460)

Co-Investigator(Kenkyū-buntansha) MUROTA Sei-itsu  Tokyo Medical and Dental University Professor, 医歯学総合研究科, 教授 (50072989)
SATOH Yasufumi  Tohoku University Professor, 医学研究科, 教授 (50178779)
NAGAI Ryozo  Tokyo University Professor, 医学系研究科, 教授 (60207975)
KODAMA Tatsuhiko  Tokyo University Professor, 先端科学技術センター, 教授 (90170266)
SHIBUYA Masabumi  Tokyo University Professor, 医学系研究科, 教授 (10107427)
Project Period (FY) 1997 – 2001
KeywordsAtherosclerosis / Vascular endothelial cell / Vasculogenesis / Angiogenesis / Vascular smooth muscle cell / Phenotypic conversion / Adhesion molecule / Oxidized LDL
Research Abstract

The Grants-in-Aid for Scientific Research on Priority Areas No. 09281104 was issued from 1997 to 2000. During the period, we organized a research group with scientists who are considered to be most active in the research field. Atherosclerosis is correlated with a variety of vascular disorders such as coronary heart disease. We therefore placed our goal on elucidation of the molecular mechanism of atherosclerosis and exploration of novel therapeutic strategies. To conduct investigation, the members were divided into 3 subgroups, i.e. Group 1, 2, and 3 with different subject of study as follows. We also formed a Central Committee to coordinate and facilitate the research activity of the subgroups.
[Group 1] Study subject : Molecular mechanism of vascular formation. Atherosclerosis has been considered to evolve according to the mechanism shared with vascular formation in the body. During the research period, we have made a significant progress in understanding vasculogenesis and angiogene … More sis. In Conclusion, the roles of new molecules such as transcription factor ets-1 and other molecules were clarified. [Group 2] Study subject : Endothelial dysfunction and blood cells. There has been accumulating evidence that atherosclerosis is initiated by endothelial dysfunction due to a variety of biological insults. We therefore formed this subgroup to explore the key molecules involved in those events. We discovered novel scavenger receptors such as LOX-1 and SRPSOX. Furthermore, we revealed that adipose tissues produce cytokines abundantly. Among those cytokines, adiponectin has been shown to play an important role in atherogenesis and insulin resistance. [Group 3] Study subject : Molecular mechanism of phenotypical conversion and proliferation of vascular smooth muscle cells. This subgroup focused on the mechanism of phenotypical conversion of vascular smooth muscle cells, which is believed to be the characteristic feature of the advanced atherosclerotic lesions. To clarify these points, a variety of transcription factors such as BTBE2 were examined. Also, the new methods to deliver genes were developed.
In conclusion, we have made a successful progress in atherosclerosis research, which will be translated into clinical application in the near future. Less

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Sano, H., Sudo, T., Yokode, M., et al.: "Functional Blockade of Platelet-derived Growth Factor Receptor-β but Not of Receptor-α Prevents Vascular Smooth Muscle Cell Accumulation in the Fibrous Cap Lesions in Apolipoprotein E-deficient Mice"Circulation. 103. 2955-2960 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshioka, A., Shirakawa, R., et al.: "Identification of protein kinase C α as an essential,but not sufficient,cytosolic factor for Ca^<2+->induced α-and dense-core granule secretion in platelets"J.Biol.Chem.. 276. 39379-39385 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Minami, M., Kume, N.et al.: "Expression of SR-PSOX,a novel cell-surface receptor for atherogenic oxidized low density lipoprotein,in human atherosclerotic lesions"Arterioscler.Thromb.Vasc.Biol.. 21. 1796-1800 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato Y.: "Role of ETS family transcription factors in vascular development and angiogenesis"Cell Struct.Funct.. 26. 19-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato, Y., Teruyama, K., et al.: "Role of transcription factors in angiogenesis: Ets-1 promotes angiogenesis as well as endothelial apoptosis"Ann.N.Y.Acad.Sci.. 947. 117-123 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teruyama, K., Abe, M., et al.: "Neuropilin-1 is a downstream target of transcription factor Ets-1 in human umbilical vein endothelial cells"FEBS Lett.. 504(1-2). 1-4 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanai H, Tanaka T, et al.: "Transforming growth factor-ss/Smads signaling induces transcription of the cell type-restricted ankyrin repeat protein CARP gene through CAGA motif in vascular smooth muscle cells"Circ Res. 88. 30-36 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sekiguchi K, Kurabayashi M, et al.: "Homeobox protein hex induces SMemb/Nonmuscle myosin heavy chain-B gene expression through the cAMP-responsive element"Circ Res. 88. 52-58 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saiura A, Sata M, et al.: "Circulating smooth muscle progenitor cells contribute to atherosclerosis"Nat Med. 7. 382-383 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sano, H., Sudo, T., Yokode, M., et al.: "Functional Blockade of Platelet-derived Growth Factor Receptor - β but Not of Receptor -α Prevents Vascular Smooth Muscle Cell Accumulation in the Fibrous Cap Lesions in Apolipoprotein E-deficient Mice."Circulation. 103. 2955-2960 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshioka, A., Shirakawa, R., et al.: "Identification of protein kinase C α as an essential, but not sufficient, cytosolic factor for Ca^<2+>-induced α - and dense-core granule secretion in platelets."J. Biol. Chem.. 276. 39379-39385 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Minami, M., Kume, N. et al.: "Expression of SR-PSOX, a novel cell-surface receptor for atherogenic oxidized low density lipoprotein, in human atherosclerotic lesions."Arterioscler. Thromb. Vasc. Biol.. 21. 1796-1800 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato Y.: "Role of ETS family transcription factors in vascular development and angiogenesis."Cell Struct. Funct.. 26. 19-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato, Y., Teruyama, K., et al.: "Role of transcription factors in angiogenesis : Ets-1 promotes angiogenesis as well as endothelial apoptosis."Ann. N. Y. Acad. Sci.. 947. 117-123 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Teruyama, K., Abe, M., et al.: "Neuropilin-1 is a downstream target of transcription factor Ets-1 in human umbilical vein endothelial cells."FEBS Lett.. 504(1-2). 1-4 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanai H, Tanaka T, et al.: "Transforming growth factor-ss/Smads signaling induces transcription of the cell type-restricted ankyrin repeat protein CARP gene through CAGA motif in vascular smooth muscle cells."Circ Res. 88. 30-36 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sekiguchi K, Kurabayashi M, et al.: "Homeobox protein hex induces Smemb/Nonmuscle myosin heavy chain-B gene expression through the cAMP-responsive element."Circ Res. 88. 52-58 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saiura A, Sata M, et al.: "Circulating smooth muscle progenitor cells contribute to atherosclerosis."Nat Med. 7. 382-383 (2001)

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

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Published: 2003-09-17  

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