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Involvements of advanced glycation end products on the developments of peripheral arterial disease in CKD patients

Research Project

Project/Area Number 18K08251
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionJuntendo University

Principal Investigator

Seiji Ueda  順天堂大学, 医学部, 准教授 (80322593)

Co-Investigator(Kenkyū-buntansha) 山岸 昌一  久留米大学, 医学部, 教授 (40281026)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords慢性腎臓病 / 動脈硬化 / 内皮障害 / 血管石灰化 / 糖化蛋白 / AGE / 血管内皮障害 / 末梢動脈疾患 / 終末糖化蛋白 / 血管新生・修復
Outline of Final Research Achievements

In the present study, we investigated the roles of AGEs in the development of vascular injury especially focusing in CKD patients with peripheral vascular disease (PAD). Serum levels of AGEs were markedly higher in CKD patients with PAD. Further, elevated AGEs levels were significantly associated with surrogate makers for atherosclerosis such as ABI and vascular calcification index in these patients. Interestingly, AGEs levels were also corelated to the incidence of sarcopenia and the severity of frail in hemodialysis patients. AGE accumulated in the gastrocnemius muscle of 5/6 nephrectomy mice in association with morphological abnormalities, capillary rarefaction, and mitochondrial dysfunction, all of which were completely inhibited by DNA-aptamer raised against AGE. Our present findings may suggest the pathological role of AGE in sarcopenia and frailty in CKD. We are now investigating the impacts of AGEs on vascular calcification using adenine-induced nephropathy model.

Academic Significance and Societal Importance of the Research Achievements

本研究では、尿毒素物質であるAGEsの血管障害における役割を検討した。大血管障害に関する影響はまだ検討中ではあるが、末梢血管の内皮障害がサルコペニア・フレイルの発症に寄与していることをはじめて明らかとし、世界に先駆けて報告した。さらには、AGEsのアプタマーの治療薬としての可能性も見出している。CKDやまたサルコペニア患者で心血管病が多発し、その生命予後も不良であることはよく知られているが、本研究の知見により新たな病態があきらかとなり、また新たな治療戦略の確立にも寄与できる可能性が高く社会的意義も高いと考える。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Fractional excretion of tumor necrosis factor receptor?1 and 2 in patients with type?2 diabetes and normal renal function2021

    • Author(s)
      Gohda Tomohito、Kamei Nozomu、Kubota Mitsunobu、Tanaka Kanako、Yamashita Yoshinori、Sakuma Hiroko、Kishida Chiaki、Adachi Eri、Koshida Takeo、Murakoshi Maki、Hagiwara Shinji、Funabiki Kazuhiko、Ueda Seiji、Suzuki Yusuke
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 12 Issue: 3 Pages: 382-389

    • DOI

      10.1111/jdi.13351

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of advanced glycation end products with sarcopenia and frailty in chronic kidney disease.2020

    • Author(s)
      Yabuuchi、J., Ueda, S., Yamagishi, S-I, Nohara, N., Nagasawa, H., Wakabayashi, K., Matsui, T., Higashimoto Y., Kadoguchi, T., Otsuka, T., Gohda, T., Suzuki, Y.
    • Journal Title

      Sci. Rep.

      Volume: 10 Issue: 1 Pages: 17647-17659

    • DOI

      10.1038/s41598-020-74673-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uremic Toxin–Targeting as a Therapeutic Strategy for Preventing Cardiorenal Syndrome2019

    • Author(s)
      Taguchi Kensei、Elias Bertha C.、Brooks Craig R.、Ueda Seiji、Fukami Kei
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 1 Pages: 2-8

    • DOI

      10.1253/circj.CJ-19-0872

    • NAID

      130007772709

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2019-12-25
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circulating kidney injury molecule‐1 as a biomarker of renal parameters in diabetic kidney disease2019

    • Author(s)
      Gohda Tomohito、Kamei Nozomu、Koshida Takeo、Kubota Mitsunobu、Tanaka Kanako、Yamashita Yoshinori、Adachi Eri、Ichikawa Saki、Murakoshi Maki、Ueda Seiji、Suzuki Yusuke
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 11 Issue: 2 Pages: 435-440

    • DOI

      10.1111/jdi.13139

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advanced glycation end products evoke inflammatory reactions in proximal tubular cells via autocrine production of dipeptidyl peptidase-42018

    • Author(s)
      Kaifu Kumiko、Ueda Seiji、Nakamura Nobutaka、Matsui Takanori、Yamada-Obara Nana、Ando Ryotaro、Kaida Yusuke、Nakata Masami、Matsukuma-Toyonaga Maki、Higashimoto Yuichiro、Fukami Kei、Suzuki Yusuke、Okuda Seiya、Yamagishi Sho-ichi
    • Journal Title

      Microvascular Research

      Volume: 120 Pages: 90-93

    • DOI

      10.1016/j.mvr.2018.07.004

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic intermittent hypoxia-mediated renal sympathetic nerve activation in hypertension and cardiovascular disease.2018

    • Author(s)
      Takahashi K, Ueda S, Kobayashi T, Nishiyama A, Fujisawa Y, Sugaya T, Shiota S, Takahashi K, Gohda T, Horikoshi S, Suzuki Y.
    • Journal Title

      Sci Rep

      Volume: 18 Issue: 1 Pages: 17926-17926

    • DOI

      10.1038/s41598-018-36159-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 尿毒素AGEsは腎不全患者サルコペニア/フレイル発症・進展へ寄与する2021

    • Author(s)
      上田誠二
    • Organizer
      第11回 日本リハビリテーション学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] CKDにおけるサルコペニア/フレイルの発症因子としてのAGE2020

    • Author(s)
      21.薮内純子、上田誠二、野原奈緒、長澤肇、大塚智之、若林啓一、鈴木祐介
    • Organizer
      第63回 日本腎臓学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Roles of chronic inflammation and AGEs in the development of vascular calcification in chronic hemodialysis patients.2019

    • Author(s)
      Otsuka T, Nagasawa H, Ueda S, Suzuki H, Yamagishi S, Suzuki Y
    • Organizer
      56th ERA-EDTA Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 透析患者におけるサルコペニア/フレイルの発症因子としてのADMA2019

    • Author(s)
      藪内純子、上田誠二、長澤肇、高橋敬子、大塚智之、鈴木祐介
    • Organizer
      第53回 日本成人病(生活習慣病)学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 透析患者の血管石灰化における終末糖化産物(AGEs)、慢性炎症の役割の解明2019

    • Author(s)
      長澤 肇、上田 誠二、薮内 純子、小林 敬、金口 泰彦、高橋 敬子、合田 朋仁、山岸 昌一、鈴木 祐介
    • Organizer
      第9回 日本腎臓リハビリテーション学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 臓器連関機序としての内因性NO合成酵素阻害物質ADMAの役割2019

    • Author(s)
      上田誠二
    • Organizer
      第19回 日本NO学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 透析患者における終末糖化蛋白AGEsと心血管病、サルコペニアとの関連の解析2019

    • Author(s)
      上田誠二、藪内純子、長澤肇、大塚智之、小林敬、海部久美子、鈴木仁、合田朋仁、松井孝憲、山岸昌一、鈴木祐介
    • Organizer
      第42回 日本高血圧学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Involvements of AGEs on vascular calcification in hemodialysis patients.2018

    • Author(s)
      Nagasawa H, Ueda S, Yabuuchi J, Kobayashi T, Kanaguchi Y, Takahashi K, Yamagishi S, Suzuki Y.
    • Organizer
      American Society of Nephrology (Kidney week 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] CKD患者において終末糖化産物(AGEs)は血管石灰化の発症に関与する.2018

    • Author(s)
      長澤 肇、上田誠二、小林敬、金口泰彦、高橋敬子、薮内純子、鈴木祐介
    • Organizer
      .第41回日本高血圧学会総会.
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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