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Searching for the mechanisms and therapeutics in the pathogenesis of stenosis after the implantation of arteriovenous ePTFE artificial and auto blood vessel grafts.

Research Project

Project/Area Number 17K09741
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionOsaka Medical College

Principal Investigator

Jin Denan  大阪医科大学, 医学研究科, 講師 (90319533)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords血管アクセス不全 / 内膜肥厚 / 線維芽細胞遊走 / 人工血管 / PTFE人工血管 / キマーゼ / キマーゼ阻害薬 / 動静脈シャント / 線維芽細胞 / 筋線維芽細胞 / 遊走 / 人工血管狭窄 / 動静脈シャント狭窄 / 機序
Outline of Final Research Achievements

We have compared the migration patterns of outside fibroblasts after subcutaneous implantation of PTFE vascular prosthesis either coated with chymase inhibitor or solvent only at 3 months after the implantation in hamsters. We found that chymase inhibitor coating tended to reduce the migration distance in the PTFE wall more than the PTFE vascular prosthesis coated solvent only, however, it did not reach a statistical significance. On the other hand, we also investigated if there is a qualitative difference between new and old version of PTFE vascular prosthesis, former adventitial interstices are modified to more narrow (20 μm) to decrease seroma after the implantation compared to old one. Although the modification of adventitial interstices in the new version of PTFE vascular prosthesis delay the migration speed of outside fibroblasts in the wall of PTFE vascular prosthesis, however, no statistical differences were found between two groups.

Academic Significance and Societal Importance of the Research Achievements

現在、腎透析によってその生命が維持されている患者さんが年々増え続けており、血液の浄化に費やされている医療費も莫大に膨れ上がっている。それに加えて、人工血管移植後のバスキュラーアクセス不全によるアクセスルートの再建術にも更なる医療費を必要とする。
また、近年、冠動脈バイパス術が年々増えており、術後の血管管腔内狭窄に対する再手術率もかなり増えている。本研究を介して、血管狭窄性疾患における動静脈中膜平滑筋細胞と外膜側の線維芽細胞のそれぞれの役割を解明し、人工血管や動静脈グラフトの血管内膜肥厚の病態生理に最も適した治療法を模索することにより基礎研究から臨床応用への橋渡しができればと考えている。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 7 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison With Mitomycin-C2019

    • Author(s)
      Nemoto E, Kojima S, Sugiyama T, Jin D, Takai S, Maeda M, Kohmoto R, Ueki M, Oku H, Ikeda T.
    • Journal Title

      Int J Mol Sci .

      Volume: 21 Issue: 1 Pages: 63-63

    • DOI

      10.3390/ijms21010063

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypermetabolism of Glutathione, Glutamate and Ornithine via Redox Imbalance in Methylglyoxal-Induced Peritoneal Injury Rats2019

    • Author(s)
      Hirahara I, Kusano E, Jin D, Takai S.
    • Journal Title

      J Biochem .

      Volume: 167 Pages: 185-194

    • DOI

      10.1093/jb/mvz077

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired function of aorta and perivascular adipose tissue in IL-18-deficient mice.2019

    • Author(s)
      Li W, Jin D, Takai S, Hayakawa T, Ogata J, Yamanishi K, Yamanishi H, Okamura H.
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 317 Issue: 5 Pages: H1142-H1156

    • DOI

      10.1152/ajpheart.00813.2018

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of a chymase inhibitor and hyaluronic acid/carboxymethylcellulose (Seprafilm) in a novel peritoneal adhesion model in rats.2019

    • Author(s)
      Ozeki M, Jin D, Miyaoka Y, Masubuchi S, Hirokawa F, Hayashi M, Takai S, Uchiyama K.
    • Journal Title

      PLoS One.

      Volume: 14 Issue: 1 Pages: e0211391-e0211391

    • DOI

      10.1371/journal.pone.0211391

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Chymase Inhibitory RNA Aptamer Improves Cardiac Function and Survival after Myocardial Infarction2019

    • Author(s)
      Jin Denan、Takai Shinji、Nonaka Yosuke、Yamazaki Satoko、Fujiwara Masatoshi、Nakamura Yoshikazu
    • Journal Title

      Molecular Therapy - Nucleic Acids

      Volume: 14 Pages: 41-51

    • DOI

      10.1016/j.omtn.2018.11.001

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of premacular mast cells in the pathogenesis of macular diseases.2019

    • Author(s)
      Sato T, Morishita S, Horie T, Fukumoto M, Kida T, Oku H, Nakamura K, Takai S, Jin D, Ikeda T.
    • Journal Title

      PLoS One.

      Volume: 14 Issue: 2 Pages: e0211438-e0211438

    • DOI

      10.1371/journal.pone.0211438

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vanin-1 in Renal Pelvic Urine Reflects Kidney Injury in a Rat Model of Hydronephrosis.2018

    • Author(s)
      Hosohata K, Jin D, Takai S, Iwanaga K.
    • Journal Title

      Int J Mol Sci.

      Volume: 19 Issue: 10 Pages: 3186-3186

    • DOI

      10.3390/ijms19103186

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel hamster nonalcoholic steatohepatitis model induced by a high-fat and high-cholesterol diet2018

    • Author(s)
      Miyaoka Y, Jin D, Tashiro K, Masubuchi S, Ozeki M, Hirokawa F, Hayashi M, Takai S, Uchiyama K.
    • Journal Title

      Experimental Animals

      Volume: 67 Issue: 2 Pages: 239-247

    • DOI

      10.1538/expanim.17-0126

    • NAID

      130006733605

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chymase inhibitor prevents the development and progression of?non-alcoholic steatohepatitis in rats fed a high-fat and high-cholesterol diet2017

    • Author(s)
      Miyaoka Yuta、Jin Denan、Tashiro Keitaro、Komeda Koji、Masubuchi Shinsuke、Hirokawa Fumitoshi、Hayashi Michihiro、Takai Shinji、Uchiyama Kazuhisa
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 134 Issue: 3 Pages: 139-146

    • DOI

      10.1016/j.jphs.2017.04.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Gelatin Hydrogel Containing Anti-Transforming Growth Factor-β Antibody in a Canine Filtration Surgery Model2017

    • Author(s)
      Maeda Michiko、Kojima Shota、Sugiyama Tetsuya、Jin Denan、Takai Shinji、Oku Hidehiro、Kohmoto Ryohsuke、Ueki Mari、Ikeda Tsunehiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 5 Pages: 985-985

    • DOI

      10.3390/ijms18050985

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Periostin antisense oligonucleotide prevents adhesion formation after surgery in mice2017

    • Author(s)
      Takai Shinji、Yoshino Masafumi、Takao Kazumasa、Yoshikawa Kazunori、Jin Denan
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 133 Issue: 2 Pages: 65-69

    • DOI

      10.1016/j.jphs.2016.10.009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗キマーゼアプタマーによる心筋梗塞後の心機能および生存率の改善効果2019

    • Author(s)
      野中 洋介、金 徳男、高井 真司、藤原 将寿、中村 義一
    • Organizer
      日本核酸医薬学会第5回年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Effect of an anti-chymase specific aptamer on cardiac function after myocardial infarction2018

    • Author(s)
      Denan Jin, Shinji Takai, Yosuke Nonaka2), Satoko Yamazaki, Masatoshi Fujiwara, Yoshikazu Nakamura
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Expression profile of mast cell chymase in stenotic lesions from patients with hemodialysis vascular access failure.2018

    • Author(s)
      Denan Jin, Hyogo Nakakura, Yoichiro Maeda, Taketoshi Kanemiya, Nobuhisa Shibahara, Shinji Takai
    • Organizer
      第90回日本薬理学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] キマーゼ阻害薬を用いたシャント狭窄予防の試み(第3報)2017

    • Author(s)
      金 徳男、金宮健翁、前田陽一郎、中倉兵庫、柴原伸久、高井真司
    • Organizer
      第62回日本透析医学会学術集会・総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 術後腹部癒着に対するペリオスチンアンチセンスオリゴヌクレオチドの有効性2017

    • Author(s)
      金 徳男、高井 真司、吉野 雅文、高尾 和正、吉川 寿徳
    • Organizer
      日本核酸医薬学会第3回年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規核酸製剤(アプタマー)によるキマーゼ阻害と心筋梗塞後の心機能改善効果2017

    • Author(s)
      金 徳男、高井真司、野中洋介、山崎聡子、藤原将寿、中村義一
    • Organizer
      第27回日本循環薬理学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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