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Elucidation of roles of MMP-1 in atherosclerosis and plaque rupture using transgenic rabbits

Research Project

Project/Area Number 26460486
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionUniversity of Yamanashi

Principal Investigator

NIIMI Manabu  山梨大学, 総合研究部, 助教 (80644898)

Co-Investigator(Kenkyū-buntansha) 西島 和俊  秋田大学, バイオサイエンス教育・研究サポートセンター, 准教授 (70435874)
Co-Investigator(Renkei-kenkyūsha) FAN Jianglin  山梨大学, 総合研究部, 教授 (60272192)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords動脈硬化 / 腹部大動脈瘤 / ウサギ / トランスジェニック / MMP-1
Outline of Final Research Achievements

Increased expression of matrix metalloprotease-1 (MMP-1) has been implicated in atherosclerosis and aneurysms; however, it is not fully understood whether macrophage-derived MMP-1 affects atherosclerosis and aneurysm. To investigate this hypothesis, we generated transgenic (Tg) rabbits expressing human MMP-1 in macrophages under the control of human scavenger receptor promoter. After feeding a cholesterol rich diet, MMP-1 Tg rabbits had similar lesion size of aortic atherosclerosis compared with non-Tg rabbits; however, Tg rabbits showed a remarkable destruction of the medial elastic lamina in the aortic lesions. Using an elastase-induced aneurysm model, we found that Tg rabbits showed grater aortic dilation than non-Tg rabbits. These results indicate that macrophage-derived MMP-1 plays an important role in pathogenesis of vascular disease.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 2015 Other

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits.2017

    • Author(s)
      Zhang, J. Niimi, M. Yang, D. Liang, J. Xu, J. Kimura, T. Mattew, A. V. Guo, Y. Fan, Y. Zhu, T. Song, J. Ackermann, R. Koike, Y. Schwendeman, A. Lai, L. Pennathur, S. Garcia-Barrio, M. Fan, J. Chen, Y. E.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: in press Issue: 6 Pages: 1068-1075

    • DOI

      10.1161/atvbaha.117.309114

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Angiotensin II Destabilizes Coronary Plaques in Watanabe Heritable Hyperlipidemic Rabbits.2016

    • Author(s)
      Li S, Wang YN, Niimi M, Ning B, Chen Y, Kang D, Wang Z, Yu Q, Waqar AB, Liu E, Zhang J, Shiomi M, Chen YE, Fan J.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 36 Issue: 5 Pages: 810-6

    • DOI

      10.1161/atvbaha.115.306871

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] ApoE knockout rabbits: A novel model for the study of human hyperlipidemia.2016

    • Author(s)
      Niimi M, Yang D, Kitajima S, Ning B, Wang C, Li S, Liu E, Zhang J, Eugene Chen Y, Fan J.
    • Journal Title

      Atherosclerosis.

      Volume: 245 Pages: 187-193

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bisphenol a exposure induces metabolic disorders and enhances atherosclerosis in hyperlipidemic rabbits.2015

    • Author(s)
      Fang, C. Ning B, Waqar AB, Niimi M, Li S, Satoh K, Shiomi M, Ye T, Dong S, Fan J:
    • Journal Title

      Journal of Applied Toxicology

      Volume: 10 Issue: 9 Pages: 1058-1070

    • DOI

      10.1002/jat.3103

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Macrophage-derived matrix metalloprotease-1 accelerates aortic aneurysm formation in transgenic rabbits2017

    • Author(s)
      Manabu Niimi, Kazutoshi Nishijima, Shuji Kitajima, Fumikazu Matsuhisa, Kaneo Satoh, Hirokazu Yamazaki, Jianglin Fan
    • Organizer
      第49回 日本動脈硬化学会総会・学術集会
    • Place of Presentation
      グランドプリンスホテル広島(広島県広島市)
    • Year and Date
      2017-07-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Hepatic overexpression of endothelial lipase reduces plasma HDL levels in transgenic rabbits2016

    • Author(s)
      Chuan Wang, Kazutoshi Nishijima, Shuji Kitajima, Manabu Niimi, Bo Ning, Jianglin Fan
    • Organizer
      第48回 日本動脈硬化学会総会・学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-07-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Angiotensin Ⅱ destabilizes coronary plaques in WHHL rabbits2016

    • Author(s)
      Shen Li, Yan-ning Wang, Manabu Niimi, Bo Ning, Yajie Chen, Dedong Kang, Ziyun Wang, Qi Yu, Ahmed Bilal Waqar, Enqi Liu, Jifeng Zhang, Masashi Shiomi, Eugene Y. Chen, Jianglin Fan
    • Organizer
      第48回 日本動脈硬化学会総会・学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-07-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] ApoE knockout rabbits: a novel model for the study of human hyperlipidemia2015

    • Author(s)
      Manabu Niimi, Bo Ning, Chuan Wang, Shen Li, Jifeng Zhang, Y. Eugene Chen, Jianglin Fan
    • Organizer
      第47回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report
  • [Presentation] CETP Deficiency in Rabbits Protects High Fat High Cholesterol Diet Induced Atherosclerosis2015

    • Author(s)
      Jifeng Zhang, Jie Xu, Jingyan Liang, Dongshan Yang, Yanhong Guo, Tianqing Zhu, Jun Song, Manabu Niimi, Liangxue Lai, Jianglin Fan, Y. Eugene Chen
    • Organizer
      Arteriosclerosis, Thrombosis and Vascular Biology/ Peripheral Vascular Disease Scientific Sessions
    • Place of Presentation
      San Francisco (USA)
    • Year and Date
      2015-05-07
    • Related Report
      2015 Research-status Report
  • [Remarks] 山梨大学大学院総合研究部医学域分子病理学講座 研究業績

    • URL

      http://www.med.yamanashi.ac.jp/clinical_basic/pathol01/publications.html

    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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