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Role of Matrix Metalloproteinase in Vascular Remodeling

Research Project

Project/Area Number 13671182
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionNagoya University

Principal Investigator

KUZUYA Masafumi  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10283441)

Co-Investigator(Kenkyū-buntansha) KANDA Shigeru  Nagoya University, University Hospital, Medical staff, 医学部附属病院, 医員
IGUCHI Akihisa  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20109763)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsMatrix Metallouroteinase / Intimal hyperplasia / vascular smooth muscle cell / MMP-2-null mutant mice / 遺伝子欠損マウス
Research Abstract

Background
Although it has been demonstrated that matrix metalloproteinases (MMPs) play an important role in the arterial remodeling in atherosclerosis and restenosis, it is not clear which MMP is involved in which process. To define the role of MMP-2 in arterial remodeling, we evaluated the influence of the targeted deletion of the MMP-2 gene on vascular remodeling after flow cessation in the murine carotid arteries.
Methods and Results
The left common carotid arteries of wild-type and MMP-2-deficient mice were ligated just proximal to their bifurcations, and the animals were then processed for morphological and biochemical studies at specific time points. MMP-2 activity and mRNA levels increased in ligated carotid arteries of wild-type mice on the basis of observation by gelatin zymography and quantitative real-time RT-PCR. There was significantly less intimal hyperplasia in MMP-2-deficient mice at 2 and 4 weeks after ligation than there in wild-type mice. Arterial explants from the aorta of MMP-2-deficient mice showed that smooth muscle cell (SMC) migration was inhibited in comparison with wild-type mice. The chemoattractant-directed invasion through a reconstituted basement membrane barrier was significantly reduced in cultured SMCs derived from MMP-2-deficient mice, although no difference was observed in SMC migration across the filter or in proliferative response between the control and MMP-2-deficient mice.
Conclusions
In a mouse carotid artery blood flow cessation model, MMP-2 contributes to intimal hyperplasia mainly through the SMC migration from the media into the intima by degrading and breaching the extracellular matrix proteins surrounding each cell and the basement membrane barrier.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Shi G-P: "Deficiency of the cysteine protease cathepsin S impairs microvessel growth"Cir.Res.. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M.: "Atorvastatin, HMG-CoA reductase inhibitor, reduces bone resorption in the elderly"J Am Ger Soc. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Umegaki H: "Identification of factors associated with long hospital stay in Japanese geriatric ward"Geriatrics Gerontology International. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda K: "Green tea catechins inhibit the cultured smooth muscle cell Invasion through the basement barrier"Atherosclerosis. 166. 23-30 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M: "Effect of aging on serum uric acid levels : longitudinal changes in a large Japanese population"Journal of Gerontology : Medical Sciences. 57. M660-M664 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M: "Changes in serum lipid levels during a 10 year period in a large Japanese population"Atherosclerosis. 163. 313-320 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M.: "Interaction of vascular endothelial cell with extracellular matrix protein : Implication of atherosclerosis and angiogenesis"Connective Tissue. 34. 309-316 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M.: "VEGF protects against oxidized LDL toxicity to endothelial cells by an intracellular glutathione-dependent mechanism through the KDR receptor"Arterioscler Thromb Vasc Biol. 21. 765-770 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M.: "Glycation cross-links inhibit matrix metalloproteinase-2 activation in vascular smooth muscle cells cultured on collagen lattice"Diabetologia. 44. 433-436 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuda Y.: "The effect of public long-term care insurance plane on care management and care planning in Japanese geriatric hospitals"Arch Gerontol.Geriat. 32. 167-177 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai S.: "Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation-dependent and independent pathways"Atherosclerosis. 155. 321-327 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueda M.: "Rise in plasma leptin levels after stimulation of hypothalamic cholinoceptive neurons by neostigmine in rats"Drugs Exptl Clin Res. 27. 185-192 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamaya N.: "Noninvolvement of hypertriglyceridemia and hyperleptinemia in blood pressure increases induced by dietary lard in rats"Drugs Exptl Clin Res.. 27. 177-184 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shi G-P, Sukhova GK, Kuzuya M, Ye Q, Du J, Zhang Y, Pan J-H, Lu M, Cheng XW, Iguchi A, Perrey S, Lee AM-E, Libby P: "Deficiency of the cysteine protease cathepsin S impairs microvessel growth"Cir Res. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M, Suzuki Y, Asai T, Koike T, Kanda S, Nakamura A, Satake S,Umegaki H, Iguchi A: "Atorvastatin, HMG-CoA reductase inhibitor, reduces bone resorption in the elderly"J Am Ger Soc. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Umegaki H, Ando F, Shimokata H, Yamamoto S, Nakamura A, Endo H, Kuzuya M, Iguchi A: "Identification of factors associated with long hospital stay in Japanese geriatric ward"Geriatrics Gerontology International. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda K, Kuzuya M, Cheng XW, Asai T, Kanda S, Tamaya-Mori N, Sasaki T, Shibata T, Iguchi A: "Green tea catechins inhibit the cultured smooth muscle cell invasion through the basement barrier"Atherosclerosis. 166. 23-30 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M, Ando F, Iguchi A, Shimokata,H: "Effect of Aging on Serum Uric Acid Levels : Longitudinal Changes in a Large Japanese Population Group"Journal of Gerontology : Medical Sciences. 57. M660-M664 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M, Ando F, Iguchi A, Shimokata H: "Changes in Serum Lipid Levels during a 10 Year Period in a Large Japanese Population : A Cross-Sectional and Longitudinal Study"Atherosclerosis. 163. 313-320 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M: "Interaction of vascular endothelial cell with extracellular matrix protein : Implication of atherosclerosis and angiogenesis"Connective Tissue. 34. 309-316 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya M, Ramos MA, Kanda S, Koike T, Asai T, Maeda K, Shitara K, Shibuya M, Iguchi A: "VEGF protects against oxidized LDL toxicity to endothelial cells by an intracellular glutathione-dependent mechanism through the KDR receptor"Arterioscler Thromb Vasc Biol. 21. 765-770 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuzuya,M., Asai,T., Kanda,S., Maeda,K., Cheng,XW., Iguchi,A: "Glycation cross-links inhibit matrix metalloproteinase-2 activation in vascular smooth muscle cells cultured on collagen lattice"Diabetologia. 44. 433-436 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuda Y, Kuzuya M, Uemura K, Yamamoto R, Endo H, Shimokata H, Iguchi A: "The effect of public long-term care insurance plane on care management and care planning in Japanese geriatric hospitals"Arch Gerontol. Geriat. 32. 167-177 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai S, Kuzuya M, Koike T, Asai T, Kanda S, Maeda K, Shibata T, Iguchi A: "Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation-dependent and independent pathways"Atherosclerosis. 155. 321-327 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueda M, Tamaya N, Miura H, Kuzuya M, Hattori A, Muraguchi M, Ohmoto Y, Iguchi A, Uemura K: "Rise in plasma leptin levels after stimulation of hypothalamic cholinoceptive neurons by neostigmine in rats"Drugs Exptl Clin Res. 27. 185-192 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamaya N, Uemura K, Yoshioka S, Ueda M, Hattori A, Kuzuya M, Ohmoto Y, Muraguchi M, Nakamura J, Iguchi A: "Noninvolvement of hypertriglyceridemia and hyperleptinemia in blood pressure increases induced by dietary lard in rats"Drugs Exptl Clin Res. 27. 177-184 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda K: "Green Tea Catechins Inhibit the Cultured Smooth Muscle Cell Invasion Through the Basement Barrier"Atherosclerosis. 166. 23-30 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuzuya M.: "Changes in Serum Lipid Levels during a 10 Year Period in a Large Japanese Population : A Cross-Sectional and Longitudinal Study"Atherosclerosis. 163. 313-320 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shi G-P: "Deficiency of the cysteine protease cathepsin S impairs microvessel growth"Cir.Res.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuzuya M.: "Interaction of vascular endothelial cell with extracellular matrix protein : Implication of atherosclerosis and angiogenesis"Connective Tissue. 34. 309-316 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuzuya M.: "Effect of Aging on Serum Uric Acid Levels : Longitudinal Changes in a Large Japanese Population Group"Journal of Gerontology : Medical Sciences. 57. M660-M664 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuzuya M.: "Atorvastatin, HMG-CoA reductase inhibitor, reduces bone resorption in the elderly"J Am Ger Soc. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ai S.: "Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation-dependent and independent pathways"Atherosclerosis. 155. 321-327 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuzuya M: "VEGF protects against oxidized LDL toxicity to endothelial cells by an intracellular glutathione-dependent mechanism through the KDR receptor"Arterioscler Thromb Vasc Biol. 21. 765-770 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuzuya M: "Glycation cross-links inhibit matrix metalloproteinase-2 activation in vascular smooth muscle cells cultured on collagen lattice"Diabetologia. 44. 433-436 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masuda Y: "The effect of public long-term care insurance plane on care management and care planning in Japanese geriatric hospitals"Arch Gerontol. Geriat. 32. 167-177 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuzuya M: "Changes in Serum Lipid Levels during a 10 Year Period in a Large Japanese Population : A Cross-Sectional and Longitudinal Study"Atherosclerosis. (In press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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