• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of new treatments with RAGE-aptamer-incorporated nanoparticles for pulmonary arterial hypertension

Research Project

Project/Area Number 18K08037
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionOkayama University

Principal Investigator

Nakamura Kazufumi  岡山大学, 医歯薬学総合研究科, 准教授 (10335630)

Co-Investigator(Kenkyū-buntansha) 赤木 達  岡山大学, 医歯薬学総合研究科, 助教 (60601127)
阪口 政清  岡山大学, 医歯薬学総合研究科, 教授 (70379840)
三好 亨  岡山大学, 大学病院, 講師 (70444651)
深水 圭  久留米大学, 医学部, 教授 (80309781)
伊藤 浩  岡山大学, 医歯薬学総合研究科, 教授 (90446047)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺高血圧症 / 終末糖化産物受容体 / RAGE / 血小板由来増殖因子 / 肺動脈平滑筋細胞 / S100A8/A9蛋白 / DNA-aptamer / モノクロタリン誘発性肺高血圧症 / S100蛋白 / 細胞増殖 / 肺動脈性肺高血圧症 / RAGE-aptamer / ナノ粒子 / 血管リモデリング
Outline of Final Research Achievements

1.Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats.: Continuous subcutaneous delivery of RAGE-aptamer suppresses development of monocrotaline-induced PAH in rats. Inhibition of RAGE ameliorates muscularization of small pulmonary arteries. Treatment with RAGE-aptamer might be a new therapeutic option for pulmonary arterial hypertension (PAH).
2.Inhibitory effects of RAGE-aptamer on proliferation of pulmonary artery smooth muscle cells (PASMCs) from patients with PAH: RAGE plays a crucial role in the inappropriate increase of PAH-PASMCs. Inhibition of RAGE signaling using RAGE aptamer inhibited the inappropriate increase of PAH-PASMCs.

Academic Significance and Societal Importance of the Research Achievements

我々を含めRAGEシグナルがPAHの病態に関与すると報告しているがRAGEシグナル抑制による治療法はまだ開発されていない。今回肺高血圧症にてRAGE特異的 DNA aptamerの有効性をしめし、RAGEシグナル抑制という世界初の治療法の開発につながる研究である。将来的に患者の予後改善・QOLの向上にもつながる日本発の治療法として発展することを期待される。

Report

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

    (36 results)

All 2021 2020 2019 2018

All Journal Article (19 results) (of which Peer Reviewed: 13 results,  Open Access: 9 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 7 results) Book (1 results)

  • [Journal Article] Efficacy of shear wave elastography for evaluating right ventricular myocardial fibrosis in monocrotaline-induced pulmonary hypertension rats2021

    • Author(s)
      Nakayama Rie、Takaya Yoichi、Nakamura Kazufumi、Kondo Megumi、Kobayashi Kaoru、Ohno Yuko、Amioka Naofumi、Akagi Satoshi、Yoshida Masashi、Miyoshi Toru、Ito Hiroshi
    • Journal Title

      Journal of Cardiology

      Volume: in press Issue: 1 Pages: 17-23

    • DOI

      10.1016/j.jjcc.2021.01.015

    • NAID

      120007189478

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemotherapy Improved Pulmonary Arterial Hypertension in a Patient with Chronic-Active Epstein-Barr Virus Infection2020

    • Author(s)
      Akagi S, Miki T, Sando Y, Fujii N, Sarashina T, Nakamura K, Ito H
    • Journal Title

      International Heart Journal

      Volume: 61 Issue: 1 Pages: 191-194

    • DOI

      10.1536/ihj.19-419

    • NAID

      130007792873

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2020-01-31
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Marked Reduction of Pulmonary Artery Pressure After Registration for Lung Transplantation Is Associated With Long-Term Survival in Patients With Pulmonary Arterial Hypertension ― Cohort Study ―2020

    • Author(s)
      Akagi S, Matsubara H, Nakamura K, Oto T, Ejiri K, Ito H
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 2 Pages: 245-251

    • DOI

      10.1253/circj.CJ-19-0784

    • NAID

      130007789878

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2020-01-24
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful Transition From Phosphodiesterase-5 Inhibitors to Riociguat Without a Washout Period in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Cohort Study2020

    • Author(s)
      Kuroda Kazuhiro、Akagi Satoshi、Nakamura Kazufumi、Sarashina Toshihiro、Ejiri Kentaro、Ito Hiroshi
    • Journal Title

      Heart, Lung and Circulation

      Volume: 29 Issue: 3 Pages: 331-336

    • DOI

      10.1016/j.hlc.2019.01.013

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Medical and surgical management of a pulmonary hypertensive adult patient with unrepaired complex congenital heart disease: a case report2020

    • Author(s)
      Akagi Satoshi、Kasahara Shingo、Akagi Teiji、Nakamura Kazufumi、Ito Hiroshi
    • Journal Title

      Journal of Congenital Cardiology

      Volume: 4 Issue: 1 Pages: 2-2

    • DOI

      10.1186/s40949-020-00033-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats2020

    • Author(s)
      Nakamura Kazufumi、Akagi Satoshi、Ejiri Kentaro、Yoshida Masashi、Miyoshi Toru、Sakaguchi Masakiyo、Amioka Naofumi、Suastika Luh Oliva Saraswati、Kondo Megumi、Nakayama Rie、Takaya Yoichi、Higashimoto Yuichiro、Fukami Kei、Matsubara Hiromi、Ito Hiroshi
    • Journal Title

      Journal of Cardiology

      Volume: - Issue: 1 Pages: 12-16

    • DOI

      10.1016/j.jjcc.2020.12.009

    • NAID

      120007182876

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 右心室および肺循環の病態生理学 特集 第6回 世界肺高血圧症学会2018のステートメントを読み解く:アンメット・メディカル・ニーズは解決されたのか?2020

    • Author(s)
      中村一文, 赤木達, 江尻健太郎, 伊藤浩
    • Journal Title

      呼吸器内科

      Volume: 37 Pages: 233-237

    • NAID

      40022182622

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Journal Article] 薬剤封入ナノ粒子を用いたDrug Delivery Systemによる肺動脈性肺高血圧の治療法開発2020

    • Author(s)
      中村一文・赤木達・伊藤浩
    • Journal Title

      Medical Science Digest

      Volume: 47 Pages: 43-45

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Role of smooth muscle cell p53 in pulmonary arterial hypertension2019

    • Author(s)
      Wakasugi Takayuki、Shimizu Ippei、Yoshida Yohko、Hayashi Yuka、Ikegami Ryutaro、Suda Masayoshi、Katsuumi Goro、Nakao Masaaki、Hoyano Makoto、Kashimura Takeshi、Nakamura Kazufumi、Ito Hiroshi、Nojiri Takashi、Soga Tomoyoshi、Minamino Tohru
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 2 Pages: e0212889-e0212889

    • DOI

      10.1371/journal.pone.0212889

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement of lung function and pulmonary hypertension after pulmonary aneurysm repair: case series2019

    • Author(s)
      Akagi Satoshi、Ejiri Kentaro、Kasahara Shingo、Nakamura Kazufumi、Ito Hiroshi
    • Journal Title

      Pulmonary Circulation

      Volume: 9 Issue: 1 Pages: 1-4

    • DOI

      10.1177/2045894019831217

    • NAID

      120006995370

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension2019

    • Author(s)
      Nakamura Kazufumi、Akagi Satoshi、Ejiri Kentaro、Yoshida Masashi、Miyoshi Toru、Toh Norihisa、Nakagawa Koji、Takaya Yoichi、Matsubara Hiromi、Ito Hiroshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 23 Pages: 5885-5885

    • DOI

      10.3390/ijms20235885

    • NAID

      120006816633

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 肺動脈性肺高血圧症 リバースリモデリングを目指した治療開発 特集:肺高血圧症2019

    • Author(s)
      中村一文、赤木達、江尻健太郎
    • Journal Title

      日本臨床

      Volume: 77 Pages: 1202-1205

    • Related Report
      2019 Research-status Report
  • [Journal Article] 肺動脈性肺高血圧症の病態,分子病態と治療の展望 特集 肺高血圧症 ガイドラインとニース会議提言を紐解く2019

    • Author(s)
      中村一文、江尻健太郎、赤木達
    • Journal Title

      呼吸器ジャーナル

      Volume: 64 Pages: 570-573

    • Related Report
      2019 Research-status Report
  • [Journal Article] Crucial role of rage in inappropriate increase of smooth muscle cells from patients with pulmonary arterial hypertension.2018

    • Author(s)
      Nakamura K, Sakaguchi M, Matsubara H, Akagi S, Sarashina T, Ejiri K, Akazawa K, Kondo M, Nakagawa K, Yoshida M, Miyoshi T, Ogo T, Oto T, Toyooka S, Higashimoto Y, Fukami K, Ito H.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 9 Pages: 1-11

    • DOI

      10.1371/journal.pone.0203046

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Progression of pulmonary artery dilatation in patients with pulmonary hypertension coexisting with a pulmonary artery aneurysm.2018

    • Author(s)
      Akagi S, Nakamura K, Sarashina T, Ejiri K, Kasahara S, Ito H.
    • Journal Title

      J Cardiol

      Volume: 71 Issue: 5 Pages: 517-522

    • DOI

      10.1016/j.jjcc.2017.11.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modern treatment to reduce pulmonary arterial pressure in pulmonary arterial hypertension.2018

    • Author(s)
      Akagi S, Matsubara H, Nakamura K, Ito H.
    • Journal Title

      J Cardiol

      Volume: 72 Issue: 6 Pages: 466-472

    • DOI

      10.1016/j.jjcc.2018.04.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Treat-and-repair strategy is a feasible therapeutic choice in adult patients with severe pulmonary arterial hypertension associated with a ventricular septal defect: Case series.2018

    • Author(s)
      Akagi S, Kasahara S, Sarashina T, Nakamura K, Ito H.
    • Journal Title

      Eur Heart J Case Rep

      Volume: 2 Issue: 2

    • DOI

      10.1093/ehjcr/yty033

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 長年のCOPD治療中に心エコー肺高血圧と右心不全を指摘され, 呼吸器内科よりコンサルトを受けた患者2018

    • Author(s)
      大塚寛昭、赤木達、中村一文
    • Journal Title

      Heart View

      Volume: 22 Pages: 215-220

    • Related Report
      2018 Research-status Report
  • [Journal Article] CTとMRI 特集 肺高血圧症Cutting Edge2018

    • Author(s)
      中村一文、松三博明、赤木達
    • Journal Title

      循環器ジャーナル

      Volume: 66 Pages: 377-381

    • Related Report
      2018 Research-status Report
  • [Presentation] TRPV2 Promotes Hypoxia-induced Pulmonary Hypertension2021

    • Author(s)
      Nakamura K
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Drug Interaction between prostaglandin I2 and endothelin receptor antagonist via IP receptor in pulmonary hypertension2021

    • Author(s)
      Akagi S, Nakamura K, Ejiri K, Ito H
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Epigenetic Effects of Hypoxia on Pathological Changes of SMCs from PAH with BMPR2 Mutation2020

    • Author(s)
      Nakamura K
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Inhibitory Effects of RAGE Aptamer on Proliferation of Smooth Muscle Cells from Pulmonary Arterial Hypertension2019

    • Author(s)
      Nakamura K
    • Organizer
      第83回日本循環器学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 肺循環の生理と肺高血圧症の病態生理からみたその治療2019

    • Author(s)
      中村一文
    • Organizer
      日本心臓血管麻酔学会 第24回学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Crucial Role of Hypoxia in Epigenetic Changes of Pulmonary Artery SMCs from PAH with BMPR2 Mutation2019

    • Author(s)
      Nakamura K
    • Organizer
      American Heart Association Scientific Sessions 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Inhibitory Effects of RAGE Aptamer on Proliferation of Smooth Muscle Cells from Pulmonary Arterial Hypertension2019

    • Author(s)
      Kazufumi Nakamura 、Satoshi Akagi 、Kentaro Ejiri 、Toru Miyoshi 、Masashi Yoshida 、Kei Fukami 、Hiroshi Ito
    • Organizer
      第 83 回日本循環器学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Heart failure and pulmonary hypertension from anticancer drugs2018

    • Author(s)
      Nakamura K
    • Organizer
      23rd Annual Scientific Meeting of the International Society of Cardiovascular Pharmacotherapy
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Reverse Right Ventricular Remodeling after Lung Transplantation in patients With PAH2018

    • Author(s)
      Nakamura K
    • Organizer
      Asian Pacific Society of Cardiology Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 肺血管のリバース リモデリングを目指した肺高血圧症の治療2018

    • Author(s)
      中村一文
    • Organizer
      第3回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 肺循環の生理と肺高血圧症の病態生理からみたその治療2018

    • Author(s)
      中村一文
    • Organizer
      第66回日本心臓病学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Hypoxia Causes Epigenetic Changes in SMCs of PAH with BMPR2 Mutation2018

    • Author(s)
      Nakamura K
    • Organizer
      The 2nd JCS Council Forum on Basic Cardio Vascular Research
    • Related Report
      2018 Research-status Report
  • [Presentation] 右心不全診療の進歩2018

    • Author(s)
      中村一文
    • Organizer
      第22回日本心不全学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Treatment for pulmonary arterial hypertension2018

    • Author(s)
      Nakamura K
    • Organizer
      2018 International Medical Symposium at Taichung Veterans General Hospital
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 病態生理からみた肺高血圧症の診断と治療2018

    • Author(s)
      中村一文
    • Organizer
      第1回日本腫瘍循環器学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 肺高血圧症の肺血管病理とCT画像2018

    • Author(s)
      中村一文
    • Organizer
      CVMW2018心血管代謝週間 (心筋生検研究会)
    • Related Report
      2018 Research-status Report
  • [Book] 肺高血圧症診療ハンドブック (分担)2020

    • Author(s)
      中村一文、赤木達
    • Total Pages
      212
    • Publisher
      中外医学社
    • ISBN
      9784498136601
    • Related Report
      2020 Annual Research Report 2019 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi