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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
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥259,200,000 (Direct Cost: ¥259,200,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥44,100,000 (Direct Cost: ¥44,100,000)
Fiscal Year 1999: ¥61,500,000 (Direct Cost: ¥61,500,000)
Fiscal Year 1998: ¥66,900,000 (Direct Cost: ¥66,900,000)
Fiscal Year 1997: ¥83,700,000 (Direct Cost: ¥83,700,000)
KeywordsAtherosclerosis / Vascular endothelial cell / Vasculogenesis / Angiogenesis / Vascular smooth muscle cell / Phenotypic conversion / Adhesion molecule / Oxidized LDL / 脈管形成 / ずり応力 / 遺伝子導入
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

Report

(6 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (54 results)

All Other

All Publications (54 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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sano, H., Sudo, T., Yokobe, 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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sato Y.: "Role of ETS family transcription factors in vascular development and angiogenesis"Cell Struct. Funct.. 26. 19-24 (2001)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saiura A, Sata M, et al.: "Circulating smooth muscle progenitor cells contribute to atherosclerosis"Nat Med. 7. 382-383 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kataoka,H.,Kume,N., et al.: "Biosynthesis and Post-translational processing of Lectin-like Oxidized low density lipoprotein Receptor-1 (Lox-1)"J Biol chem.. 275. 6573-6579 (2000)

    • Related Report
      2000 Annual Research Report
  • [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. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsumoto K,Hirano K-I,Nozaki S, et al.: "Expression of macrophage (Mφ) scavenger receptor, CD36, in cultured human aortic smooth muscle cells in association with expression of peroxisome proliferator activated receptor-γ, which regulates gain of Mφ-like phenotype in vitro, and its implication in atherogenesis"Arterioscler Thromb Vasc Biol. 20. 1027-1032 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanaki T,Morisaki N,Bujo H, et al.: "The regulatory expression of procollagen COOH-terminal proteinase enhancer in the proliferation of vascular smooth muscle cells"Biochem Biophys Res Commun. 270. 1049-54 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Namba,K.,Abe,M.,Saito,S., et al.: "Indispensable role of the transcription factor PEBP2/CBF in angiogenic activity of a murine endothelial cell MSS31"Oncogene. 19. 173-179 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hoshino Y,Kurabayashi M,Nagai R et al.: "Regulated expression of the BTEB2 transcription factor in vascular smooth muscle cells : analysis of developmental and pathological expression profiles shows implications as a predictive factor for restenosis."Circulation. 102(20). 2528-34 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Tamura,Y.Ogawa,H.Chusho, et al.: "Cardiac fibrosis in mice lackingbrain natriuretic peptide"Proc.Natl.Acad.Sci.USA. 97(8). 4239-44 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oda, N., Abe, M., Sato, Y.: "ETS-1 converts endothelial cells to the angiogenic phenotype by inducing the expression of matrix metalloproteinases and integrin β3"J. Cell Physiol.. 178(2). 121-132 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takahashi T., Ueno H. et al.: "VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells"Oncogene. 18(13). 2221-2230 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kanaki, T., Bujo, H. et al.: "Expression of LR11, a mosaic LDL receptor family member, is markedly increased in atherosclerotic lesions"Arterioscler. Thromb. Vasc. Biol.. 19. 2687-2695 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kataoka, H., Kume, N. et al.: "Expression of lectin-like oxidized LDL receptor-1 in human atherosclerotic lesions"Circulation. 99(24). 3110-3117 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nkata A., Nakagawa Y. et al.: "CD36, a novel receptor for oxidized low density liporotein, is highly expressed on lipid-laden macrophages in human atherosclerotic aorta ; differential contribution of CD36 and scavenger receptors to atherogenesis"Arterioscler Thromb Vasc Biol. 19. 1333-1339 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawai-Kowase, K., Kurabayashi, M. et al.: "Transcriptional activation of the zinc finger transcription factor BTEB2 gene by Egr-1 through mitogen-activated protein kinase pathways in vascular smooth muscle cells"Circ. Res.. 787-795

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwasaka,C.et al.: "Ets-1 regualtes angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells." J.Cell.Physiol.169. 522-531 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wakiya,K.et al.: "A cyclic AMP response element and an ETS motif are involved in the transcreptional regulation flt-1 tyrosine kinase (VEGF receptor 1) gene." J.Biol.Chem.271. 30823-30828 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki,T.et al.: "Preferential differeniation of P19 mouse embryonal carcinoma cells into smooth muscle cells; use of retinoic acid and antisense against the central nervous system-specific POU transcription factor Bm-2" Circulation Research. 78. 395-404 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe,M.et al.: "Tandem elements of CCTCCC are required for the cell-type-specific expression of the mouse smooth muscle myosin heavy chain gene (SM1/2) promoter." Circulation Research. 78. 978-989 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakai,A.et al.: "P-Selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocytes" Arterioscler Thromb Vasc Biol.17. 310-316 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishi,E.et al.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation research. 80. 638-644 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iwasaka,C.et al.: "Ets-1 regualtes angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells." J.Cell.Physiol.169. 522-531 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Wakiya,K.et al.: "A cyclic AMP response element and an ETS motif are involved in the transcreptional regulation 0 flt-1 tyrosine kinase (VEGF receptor 1) gene." J.Biol.Chem.271. 30823-30828 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki,T.et al.: "Preferential differeniation of P19 mouse embryonal carcinaoma cells into smooth muscle cells ; use of retinoic acid and antisense against the central nervous system-specific POU transcription factor Bm-2." Circulation Research. 78. 395-404 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe,M.et al.: "Tandem elements of CCTCCC are required for the cell-type-specific expression of the mouse smooth muscle myosin heavy chain gene (SM1/2) promoter." Circulation Research. 78. 978-989 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakai,A.et al.: "P-Selectin and vascullar cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocytes." Arterioscler Thromb Vasc Biol.17. 310-316 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishi,E.et al.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation research. 80. 638-644 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kuro-o,M.et al.: "Mutation of the mouse klotho gene leads to a syndrome resembling ageing." Nature. 390. 45-51 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ochi,H., et al.: "Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatidylcholine in cultured endothelial cells." Biochem.Biophys.Res.Commun.(in press).

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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