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Investigation of coronary vascular reaction and complication after stent implantation using mini pigs with human-like unstable atherosclerotic lesions

Research Project

Project/Area Number 17K09595
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionNihon University

Principal Investigator

LI Yuxin  日本大学, 医学部, 准教授 (30599048)

Co-Investigator(Kenkyū-buntansha) 高山 忠輝  日本大学, 医学部, 教授 (10366601)
羽尾 裕之  日本大学, 医学部, 教授 (40393243)
松本 太郎  日本大学, 医学部, 教授 (50366580)
平山 篤志  日本大学, 医学部, 教授 (50459880)
春田 裕典  日本大学, 医学部, 助教 (90754002)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords分子血管学 / 大動物モデル / 大動物実験 / 動脈硬化 / ステント / 合併症 / ステント留置後合併症
Outline of Final Research Achievements

To observe vascular reaction and complications after catheter intervention therapy for patients with ischemic heart disease such as angina and myocardial infarction, two different types of stents were placed at the site of coronary atherosclerotic lesions in LDL cholesterol receptor deficiency (LDLR-/-) minipig. No significant stenosis was observed at the site of stent placement 3 months after stent implantation, but mild to moderate stenosis was observed 12 months after stent implantation. Inflammatory cell infiltration scattered in the neointimal, fibrin accumulation around the strut, fragmented calcification and foamy macrophages were observed in the neointimal in both groups. Twelve months after stent implantation, a neointimal layer mainly composed of smooth muscle cells was formed at the placement site. Inside the layer of smooth muscle cells, neoatherosclerosis, which including lipid pool, macrophage infiltration, necrotic region, and calcification deposition, was observed.

Academic Significance and Societal Importance of the Research Achievements

ステント留置後の慢性期合併症が現在の解決問題となっているが、臨床で実際に使用する前に認識されなかった。また異なるステントによる留置後の合併症の相違が不明である。その理由は適切な動物モデルがなかったため、実験で事前に詳しい検討ができなかったことである。本研究で使用する遺伝子組換えブタモデルはヒトと高い類似性の冠動脈粥腫病変を持ち、ステント留置後の血管反応も虚血患者の血管反応と類似していた。このモデルを用いて異なるステントを病変部位に留置し、短期間に血管反応を比較観察することができる。また新規ステントの安全性と有効性を検証することにより、新たなステントの開発に繋がる。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (41 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (34 results) (of which Int'l Joint Research: 11 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Effect of Rivaroxaban and Clopidogrel Combination Therapy on In-Stent Responses After Everolimus-Eluting Stent Implantation in a Porcine Coronary Model2022

    • Author(s)
      Kitano Daisuke、Migita Suguru、Li Yuxin、Takahashi Rie、Taniguchi Yoshiki、Kurosawa Takafumi、Sudo Mitsumasa、Haruta Hironori、Hiro Takafumi、Takayama Tadateru、Mitsumata Masako、Matsumoto Taro、Okumura Yasuo、Hirayama Atsushi
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 29 Issue: 1 Pages: 69-81

    • DOI

      10.5551/jat.56549

    • NAID

      130008138818

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2022-01-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathological findings after third- and second-generation everolimus-eluting stent implantations in coronary arteries from autopsy cases and an atherosclerotic porcine model2021

    • Author(s)
      Migita Suguru、Kitano Daisuke、Li Yuxin、Koyama Yutaka、Shimodai-Yamada Sayaka、Onishi Akira、Fuchimoto Daiichiro、Suzuki Shunichi、Nakamura Yoshiyuki、Matsuyama Taka-aki、Hirota Seiichi、Sakuma Masashi、Tsujimoto Masahiko、Hirayama Atsushi、Okumura Yasuo、Hao Hiroyuki
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 6281-6281

    • DOI

      10.1038/s41598-021-85740-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of the dipeptidyl peptidase-4 inhibitor linagliptin on atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbits: iMap-IVUS and pathological analysis2020

    • Author(s)
      Kurosawa Takafumi、Li Yuxin、Sudo Mitsumasa、Haruta Hironori、Hagikura Kazuhiro、Takayama Tadateru、Hiro Takafumi、Shiomi Masashi、Hao Hiroyuki、Matsumoto Taro、Hirayama Atsushi、Okumura Yasuo
    • Journal Title

      Heart and Vessels

      Volume: 36 Issue: 1 Pages: 127-135

    • DOI

      10.1007/s00380-020-01689-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The neovascularization effect of dedifferentiated fat cells2020

    • Author(s)
      Watanabe Hirofumi、Goto Shumpei、Kato Reona、Komiyama Shogo、Nagaoka Yuki、Kazama Tomohiko、Yamamoto Chii、Li Yuxin、Konuma Noriyoshi、Hagikura Kazuhiro、Matsumoto Taro
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 9211-9211

    • DOI

      10.1038/s41598-020-66135-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuroprotection Mediated by Upregulation of Endothelial Nitric Oxide Synthase in Rho-Associated, Coiled-Coil-Containing Kinase 2 Deficient Mice2018

    • Author(s)
      Hiroi Y, Noma K, Kim HH, Sladojevic N, Tabit CE, Li Y, Soydan G, Salomone S, Moskowitz MA, Liao JK.
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 4 Pages: 1195-1204

    • DOI

      10.1253/circj.CJ-17-0732

    • NAID

      130006528549

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of plaque progression and promotion of plaque stability by glucagon-like peptide-1 receptor agonist: Serial in vivo findings from iMap-IVUS in Watanabe heritable hyperlipidemic rabbits.2017

    • Author(s)
      Sudo M, Li Y, Hiro T, Takayama T, Mitsumata M, Shiomi M, Sugitani M, Matsumoto T, Hao H, Hirayama A.
    • Journal Title

      Atherosclerosis

      Volume: 265 Pages: 283-291

    • DOI

      10.1016/j.atherosclerosis.2017.06.920

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] マウス皮膚再生過程に出現する成熟脂肪細胞由来線維芽様細胞の形質解析2021

    • Author(s)
      風間智彦、石川三友紀、山元智衣、長岡悠紀、萩倉一博、 李予昕、松本太郎.
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脱分化脂肪細胞(DFAT)を用いた下肢血管再生治療の実用化2021

    • Author(s)
      松本太郎、風間智彦、李予昕、萩倉一博、山元智衣、長岡悠紀、坂利江、加藤礼保納、加野浩一郎、河野通成、樫村勉、前田英明、副島一孝、田中正史
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 重症下肢虚血に対する自家脱分化脂肪細胞移植によるFirst-in-Human臨床研究2021

    • Author(s)
      松本太郎、風間智彦、李予昕、萩倉一博、山元智衣、長岡悠紀、坂利江、河野通成、前田英明、樫村勉、副島一孝、田中正史
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Pathology of Coronary Artery After Third generation Abluminal Biodegradable-polymer Drug-eluting Stent Implantation in Atherosclerotic Porcine Model.2020

    • Author(s)
      Suguru Migita, Daisuke Kitano, Yuxin Li, Yutaka Koyama, Akira Onishi, Daiichiro Fuchimoto, Shunichi Suzuki, Yoshiyuki Nakamura, Atsushi Hirayama, Yasuo Okumura, Hiroyuki Hao.
    • Organizer
      Scientific Sessions 2020 of American Heart Association
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathology of In-stent Neointima in Atherosclerotic Porcine Peripheral Artery Treated by Drug coated Balloon.2020

    • Author(s)
      Suguru Migita, Daisuke Kitano, Yutaka Koyama, Yuxin Li, Atsushi Hirayama, Yasuo Okumura, Hiroyuki Hao.
    • Organizer
      Scientific Sessions 2020 of American Heart Association
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathology of coronary artery after drug-eluting stent implantation in low-density lipoprotein receptor knockout pigs; comparison with wild type pigs.2020

    • Author(s)
      3.Suguru Migita1, Daisuke Kitano, Yuxin Li, Sayaka Yamada, Toshio Mukaiyama, Akira Onishi, Daiichiro Fuchimoto, Shunichi Suzuki, Yoshiyuki Nakamura, Atsushi Hirayama, Yasuo Okumur, Hiroyuki Hao.
    • Organizer
      88th ESC Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endothelial-specific Ablation of Non-nuclear Estrogen Receptor alpha Signaling Deteriorates Vascular Remodeling Response.2020

    • Author(s)
      P.Y Liu, N Fukuma, Y Hiroi, K Ueda, T Kariya, G Numata, Y Adachi, M Toyoda, Y Li, K Noma, H Toko, Y Kanai, E Takimoto, J.K Liao, I Komuro.
    • Organizer
      ESC Congress 2020; The Digital Experience
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathology of coronary artery after third-generation drug-eluting stent implantation in low-density lipoprotein receptor knockout pigs and human autopsy cases.2020

    • Author(s)
      Suguru Migita, Daisuke Kitano, Yuxin Li, Yutaka Koyama, Sayaka Shimodai-Yamada, Akira Onishi, Daiichiro Fuchimoto, Shunichi Suzuki, Yoshiyuki Nakamura, Atsushi Hirayama, Yasuo Okumura, Hiroyuki Hao.
    • Organizer
      88th ESC Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathology of Coronary Artery after Third-Generation Drug-Eluting Stent Implanation in Atherosclerotic Procine Model and Human Autopsy Cases.2020

    • Author(s)
      Suguru Migita, Daisuke Kitano, Yuxin Li, Sayaka Yamada, Kumiko Asakura, Toshio Mukaiyama, Akira Onishi, Daiichiro Fuchimoto, Shunichi Suzuki, Yoshiyuki Nakamura, Yasuo Okumura, Hiroyuki Hao.
    • Organizer
      American College of Cardiology (ACC) 2020 Annual Scientific Session.
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス皮膚欠損修復過程における成熟脂肪細胞の脱分化現象及び組織修復に関する検討2020

    • Author(s)
      石川三友紀、長岡悠紀、萩倉 一博、風間 智彦、李 予昕、松本太郎.
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 日本大学医学部リサーチセンターCPFにおけるDFAT細胞加工製品の製造2020

    • Author(s)
      風間 智彦、 山元 智衣、長岡 悠紀:、萩倉 一博、李予昕、副島 一孝、松本 太郎.
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 治療用細胞としてのDFATの保存条件の検討2020

    • Author(s)
      長岡 悠紀、 風間 智彦、山元 智衣、萩倉 一博、 李 予昕、副島 一孝、松本 太郎.
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ブタを用いた造腫瘍性試験に関する検討2020

    • Author(s)
      佐野 太一、李 予昕、風間 智彦、萩倉 一博、鈴木 俊一、淵本 大一郎、三角 浩司、大西 彰、加野 浩一郎、松本 太郎.
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 日本大学医学部リサーチセンターCPFにおける清浄区域の設定と環境モニタリングについて2020

    • Author(s)
      山元 智衣、風間 智彦、長岡 悠紀、大野 聡子、李 予昕、萩倉 一博、松本 太郎.
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 遺伝子組換え医学用モデル豚のミニブタ化と精子および受精卵凍結保存方法の開発2020

    • Author(s)
      中村嘉之、瀧沢慶太、李予昕、大西 彰、三角浩二、岩元 正樹、淵本大一郎.
    • Organizer
      日本畜産学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Pathology of Coronary Artery after Third-Generation Drug-Eluting Stent Implanation in Atherosclerotic Procine Model and Human Autopsy Cases.2020

    • Author(s)
      1.Suguru Migita, Daisuke Kitano, Yuxin Li, Sayaka Yamada, Kumiko Asakura, Toshio Mukaiyama, Akira Onishi, Daiichiro Fuchimoto, Shunichi Suzuki, Yoshiyuki Nakamura, Yasuo Okumura, Hiroyuki Hao.
    • Organizer
      American College of Cardiology (ACC) 2020 Annual Scientific Session.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝子組換え医学用モデル豚のミニブタ化と精子および受精卵凍結保存方法の開発2020

    • Author(s)
      1.中村嘉之、瀧沢慶太、李予昕、大西 彰、三角浩二、岩元 正樹、淵本大一郎.
    • Organizer
      日本畜産学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 大動物モデルを用いた冠動脈不安定プラークに対する治療戦略2020

    • Author(s)
      李予昕
    • Organizer
      山梨大学医学部分子病理学講演会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Comparison of In-Stent Responses Between Durable Polymer and Bioabsorbable Polymer Everolimus-Eluting Stent in a Human-Like Coronary Atherosclerotic Porcine Model.2019

    • Author(s)
      2.Daisuke Kitano, Yuxin Li, Suguru Migita, Hiroyuki Hao, Atsushi Hirayama, Yasuo Okumura.
    • Organizer
      Scientific Sessions 2019 of American Heart Association
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 医学用モデル豚の小型化と生殖細胞凍結保存方法の開発2019

    • Author(s)
      中村嘉之、瀧沢慶太、李予昕、淵本大一郎.
    • Organizer
      繁殖衛生セミナー
    • Related Report
      2019 Research-status Report
  • [Presentation] 免疫不全ブタを用いた再生医療等製品の造腫瘍性試験2019

    • Author(s)
      佐野 太一、李 予昕、風間 智彦、長岡 悠紀、萩倉 一博、山元 智衣、鈴木 俊一、淵本 大一郎、三角 浩司、大西 彰、加野浩一郎、松本 太郎.
    • Organizer
      第7回日本先進医工学ブタ研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 医学用モデル豚の小型化と生殖細胞凍結保存方法の開発高コレステロール・動脈硬化症ブタの小型化と生殖細胞凍結保存方法の検討2019

    • Author(s)
      中村嘉之、瀧沢慶太、李予昕、淵本大一郎.
    • Organizer
      日本養豚学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 免疫不全ブタを用いた造腫瘍性評価法の検討2019

    • Author(s)
      佐野 太一,李 ヨキン,風間 智彦,長岡 悠紀,萩倉 一博,山元 智衣,鈴木 俊一,淵本大一郎,三角 浩司,大西  彰,加野浩一郎,松本 太郎.
    • Organizer
      第40回日本炎症・再生医学会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス皮膚欠損治癒過程における成熟脂肪細胞の形質変換および組織再生に関する検討2019

    • Author(s)
      石川三友紀,萩倉 一博,風間 智彦,李 ヨキン,松本 太郎.
    • Organizer
      第40回日本炎症・再生医学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 免疫不全ブタを用いたヒト脱分化脂肪細胞移植安全性試験2019

    • Author(s)
      佐野 太一、李 予昕、風間 智彦、長岡 悠紀、萩倉 一博、山元 智衣、鈴木 俊一、淵本 大一郎、三角 浩司、大西 彰、加野浩一郎、松本 太郎
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス皮膚欠損治癒過程における成熟脂肪細胞の形質転換に関する検討。2019

    • Author(s)
      石川三友紀、松本太郎、李 予昕、萩倉 一博、風間 智彦
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス皮膚欠損治癒過程における成熟脂肪細胞の形質転換に関する検討2019

    • Author(s)
      石川三友紀、松本太郎、李 予昕、萩倉 一博、風間 智彦
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 免疫不全ブタを用いたヒト脱分化脂肪細胞移植安全性試験2019

    • Author(s)
      佐野 太一、李 予昕、風間 智彦、長岡 悠紀、萩倉 一博、山元 智衣、鈴木 俊一、淵本 大一郎、三角 浩司、大西 彰、加野浩一郎、松本 太郎.
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Aging and Coronary Artery Atherosclerosis: Insight from Clinical Intravascular Imaging Observation and Large Animal Model.2018

    • Author(s)
      Yuxin Li, Taro Matsumoto, Atsushi Hirayama.
    • Organizer
      Asian Pacific Society of Cardiology Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 免疫不全ブタを用いたヒト脱分化脂肪細胞移植安全性試験2018

    • Author(s)
      佐野 太一、李 予昕、風間 智彦、長岡 悠紀、萩倉 一博、山元 智衣、鈴木 俊一、淵本 大一郎、三角 浩司、大西 彰、松本 太郎
    • Organizer
      第6回日本先進医工学ブタ研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Role of Rho-associated Coiled-coil Containing Kinases in Mediating Age-related Vascular Stiffening and Hypertension.2018

    • Author(s)
      Yuxin Li, Haw-Chih Tai, Soeun Ngoy, Nikola Sladojevic, Hyung-Hwan Kim, James K. Liao
    • Organizer
      Scientific Sessions 2018 of American Heart Association.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A Novel Large Animal Model of Accelerated Human-Like Coronary In-stent Neoatherosclerosis Formation.2017

    • Author(s)
      Yuxin Li, Hironori Haruta, Daiichiro Fuchimoto, Shunichi Suzuki, Kazumi Satou, Daisuke Kitano, Tadateru Takayama, Takafumi Hiro, Rika Kawakami, Seiichi Hirota, Taro Matsumoto, Hiroyuki Hao, Akira Onishi, Atsushi Hirayama.
    • Organizer
      Scientific Sessions 2017 of American Heart Association
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of early statin treatment before atherosclerosis formation on plaque stability2017

    • Author(s)
      Yuxin Li; Akira Onishi; Mitsumasa Sudo; Hironori Haruta; Tadateru Takayama; Shunichi Suzuki; Daiichiro Fuchimoto; Shoichiro Sembon; Masaki Iwamoto; Michiko Hashimoto; Takafumi Hiro; Taro Matsumoto; Masako Mitsumata; Masahiko Sugitani; Atsushi Hirayama
    • Organizer
      日本大学学部連携シンポジュウム
    • Related Report
      2017 Research-status Report
  • [Presentation] ステント開発におけるヒト不安定粥腫類似病変を持つLDL受容体欠損ミニブタの利用2017

    • Author(s)
      李予昕、大西彰、淵本大一郎、鈴木俊一、佐野太一、羽尾裕之、松本太郎、平山篤志.
    • Organizer
      第5回日本先進医工学ブタ研究会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 高コレステロール血症/動脈硬化症モデルミニブタ2020

    • Inventor(s)
      中村嘉之, 瀧沢慶太, 淵本大一郎, 李ヨキンなど
    • Industrial Property Rights Holder
      中村嘉之, 瀧沢慶太, 淵本大一郎, 李ヨキンなど
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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