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

The possibility of pleiotropic effects of Novel Oral Anticoagulants (NOAC) on Rho-kinase-cyclophilin A System

Research Project

Project/Area Number 25670379
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionTohoku University

Principal Investigator

SHIMOKAWA Hiroaki  東北大学, 医学(系)研究科(研究院), 教授 (00235681)

Co-Investigator(Kenkyū-buntansha) SATOH Kimio  東北大学, 高度教養教育・学生支援機構, 准教授 (80436120)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsシグナル伝達 / スタチン / 低分子量G蛋白 / サイクロフィリンA / 心血管疾患 / 平滑筋増殖 / バイオマーカー / Rhoキナーゼ / 新規抗凝固薬 / Xa阻害薬
Outline of Final Research Achievements

We tested our hypothesis that small GTP-binding protein GDP dissociation stimulator (SmgGDS) plays a crucial role in the molecular mechanisms of the Rac1 signaling pathway inhibition by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in endothelial cells. In the present study, we demonstrated that statins exert their pleiotropic effects through SmgGDS upregulation with a resultant Rac1 degradation and reduced oxidative stress in animals and humans.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (31 results)

All 2015 2014 2013 Other

All Journal Article (21 results) (of which Peer Reviewed: 20 results,  Open Access: 17 results,  Acknowledgement Compliant: 14 results) Presentation (3 results) (of which Invited: 3 results) Book (3 results) Remarks (1 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Journal Article] PDE1C negatively regulates growth factor receptor degradation and promotes vascular smooth muscle cell proliferation.2015

    • Author(s)
      Satoh K, Kikuchi N, Kurosawa R, Shimokawa H.
    • Journal Title

      Circ Res.

      Volume: 116 Issue: 7 Pages: 1098-1100

    • DOI

      10.1161/circresaha.115.306139

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cyclophilin A in Cardiovascular Homeostasis and Diseases2015

    • Author(s)
      Satoh K
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 235 Issue: 1 Pages: 1-15

    • DOI

      10.1620/tjem.235.1

    • NAID

      130004822422

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 2014 Williams Harvey Lecture: importance of coronary vasomotion abnormalities-from bench to bedside.2014

    • Author(s)
      Shimokawa H.
    • Journal Title

      Eur Heart J.

      Volume: 35 Issue: 45 Pages: 3180-3193

    • DOI

      10.1093/eurheartj/ehu427

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Basigin mediates pulmonary hypertension by promoting inflammation and vascular smooth muscle cell proliferation2014

    • Author(s)
      Satoh K, Satoh T, Kikuchi N, Omura J, Kurosawa R, Suzuki K, Sugimura K, Aoki T, Nochioka K, Tatebe S, Yamamoto S, Miura M, Shimizu T, Ikeda S, Yaoita N, Fukumoto Y, Minami T, Miyata S, Nakamura K, Ito H, Kadomatsu K, Shimokawa H.
    • Journal Title

      Circ Res.

      Volume: 115 Issue: 8 Pages: 738

    • DOI

      10.1161/circresaha.115.304563

    • URL

      https://pure.teikyo.jp/en/publications/e90bf195-816e-43b9-b666-f1f2f5351b17

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Vascular function.2014

    • Author(s)
      Shimokawa H, Satoh K.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 34 Issue: 11 Pages: 2359-2362

    • DOI

      10.1161/atvbaha.114.304119

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Light and dark of reactive oxygen species for vascular function.2014

    • Author(s)
      Shimokawa H, Satoh K.
    • Journal Title

      J Cardiovasc Pharmacol.

      Volume: 65

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] High-sensitivity C-reactive protein: still need for next-generation biomarkers for remote future cardiovascular events.2014

    • Author(s)
      Satoh K, Shimokawa H.
    • Journal Title

      Eur Heart J.

      Volume: 35 Issue: 27 Pages: 1776-1778

    • DOI

      10.1093/eurheartj/ehu115

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dual roles of vascular-derived reactive oxygen species-With a special reference to hydrogen peroxide and cyclophilin A2014

    • Author(s)
      Kimio Satoh, Shigeo Godo, Hiroki Saito, Budbazar Enkhjargal, Hiroaki Shimokawa
    • Journal Title

      Journal of molecular and cellular cardiology

      Volume: (In press) Pages: 50-56

    • DOI

      10.1016/j.yjmcc.2013.12.022

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Globotriaosylceramide induces endothelial dysfunction in Fabry disease.2014

    • Author(s)
      Satoh K.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 34 Issue: 1 Pages: 2-4

    • DOI

      10.1161/atvbaha.113.302744

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Crucial role of rho-kinase in pressure overload-induced right ventricular hypertrophy and dysfunction in mice2014

    • Author(s)
      Ikeda, S., Satoh, K., Kikuchi, N., Miyata, S., Suzuki, K., Omura, J., Shimizu, T., Kobayashi, K., Kobayashi, K., Fukumoto, Y., Sakata, Y., and Shimokawa, H.
    • Journal Title

      Arterioscler. Thromb. Vasc Biol.

      Volume: 34 Issue: 6 Pages: 1260

    • DOI

      10.1161/atvbaha.114.303320

    • URL

      https://pure.teikyo.jp/en/publications/3fbbdae8-b5d4-4570-ba4d-752270db4b24

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination therapy with fasudil and sildenafil ameliorates monocrotaline-induced pulmonary hypertension and survival in rats.2014

    • Author(s)
      Elias-Al-Mamun M, Satoh K, Tanaka S, Shimizu T, Nergui S, Miyata S, Fukumoto Y, Shimokawa H.
    • Journal Title

      Circ J.

      Volume: 78 Pages: 967-976

    • NAID

      130003391036

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Endothelial AMPK regulates blood pressure and coronary flow responses through hyperpolarization mechanism in mice.2014

    • Author(s)
      Enkhjargal B, Godo S, Sawada A, Nergui S, Saito H, Noda K, Satoh K, Shimokawa H.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 34 Issue: 7 Pages: 1505-1513

    • DOI

      10.1161/atvbaha.114.303735

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Platelets are highly activated in patients of chronic thromboembolic pulmonary hypertension2014

    • Author(s)
      Yaoita N, Shirakawa R, Fukumoto Y, Sugimura K, Miyata S, Miura Y, Nochioka K, Miura M, Tatebe S, Aoki T, Miyamichi-Yamamoto S, Satoh K, Kimura T, Shimokawa H, Horiuchi H.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 34 Issue: 11 Pages: 2486

    • DOI

      10.1161/atvbaha.114.304404

    • URL

      https://pure.teikyo.jp/en/publications/1cd583b9-53c8-43fb-9623-40a38c842780

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enhanced [18F]fluorodeoxyglucose accumulation in the right ventricular free wall predicts long-term prognosis of patients with pulmonary hypertension: a preliminary observational study.2014

    • Author(s)
      Tatebe S, Fukumoto Y, Oikawa-Wakayama M, Sugimura K, Satoh K, Miura Y, Aoki T, Nochioka K, Miura M, Yamamoto S, Tashiro M, Kagaya Y, Shimokawa H.
    • Journal Title

      Eur Heart J Cardiovasc Imaging.

      Volume: 15 Issue: 6 Pages: 666-672

    • DOI

      10.1093/ehjci/jet276

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] OCT imaging for the management of pulmonary hypertension.2014

    • Author(s)
      Dai Z, Fukumoto Y, Tatebe S, Sugimura K, Miura Y, Nochioka K, Aoki T, Miyamichi-Yamamoto S, Yaoita N, Satoh K, Shimokawa H.
    • Journal Title

      JACC-Cardiovasc Imaging.

      Volume: 7 Issue: 8 Pages: 843-845

    • DOI

      10.1016/j.jcmg.2014.01.020

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Visualization of Complete Regression of Pulmonary Arterial Remodeling on Optical Coherence Tomography in a Patient With Pulmonary Arterial Hypertension.2014

    • Author(s)
      Dai Z, Sugimura K, Fukumoto Y, Tatebe S, Miura Y, Nochioka K, Aoki T, Miyamichi-Yamamoto S, Yaoita N, Satoh K, Shimokawa H.
    • Journal Title

      Circ J.

      Volume: 78 Pages: 2771-2773

    • NAID

      130004700253

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Extracorporeal low-energy shock wave therapy exerts anti-inflammatory effects in acute myocardial infarction in rats in vivo.2014

    • Author(s)
      Abe Y, Ito K, Hao K, Shindo T, Ogata T, Kagaya Y, Kurosawa R, Nishimiya K, Satoh K, Miyata S, Kawakami K, Shimokawa H.
    • Journal Title

      Circ J.

      Volume: 78 Pages: 2915-2925

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Statins exert pleiotropic effects through SmgGD S up-regulation with a resultant Rac l degradation2013

    • Author(s)
      Tanaka S, Fukumoto Y, Nochioka K, Minami T, Kudo S, Shiba N, Takai Y, Williams CL, Liao JK, Shimokawa H
    • Journal Title

      Arterioscter Thromz Vasc Biol

      Volume: (in press) Issue: 7 Pages: 1591-1600

    • DOI

      10.1161/atvbaha.112.300922

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications and prognostic impact -Multicenter registrystudy of the Japanese Coronary Spasm Association-2013

    • Author(s)
      Takagi Y, Yasuda S, Takahashi J, TsunodaR, Ogata Y, Seki A, Sumiyoshi T, Matsui M, Goto T, Tanabe Y, Sueda S, Sato T, Ogawa S, Kubo N, Momomura S, Ogawa H, Shimokawa H
    • Journal Title

      Eur Heart J

      Volume: 34 Issue: 4 Pages: 258-267

    • DOI

      10.1093/eurheartj/ehs199

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Plasma Cyclophilin A Is a Novel Biomarker for Coronary Artery Disease2013

    • Author(s)
      Satoh K, Fukumoto Y, Sugimura K, Miura Y, Aoki T, Nochioka K, Tatebe S, Miyamichi-Yamamoto S, Shimizu T, Osaki S,Takagi Y, Tsuburaya R, Ito Y, Matsumoto Y, Nakayama M, Takeda M, Takahashi J, Ito K, Yasuda S, Shimokawa H
    • Journal Title

      Circulation Journal

      Volume: 77 Issue: 2 Pages: 447-455

    • DOI

      10.1253/circj.CJ-12-0805

    • NAID

      10031138924

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dipeptidyl Peptidase-4 Inhibitors2013

    • Author(s)
      佐藤公雄 (Kimio Satoh)
    • Journal Title

      Circulation Journal

      Volume: 77 Issue: 5 Pages: 1156-1157

    • DOI

      10.1253/circj.CJ-13-0064

    • NAID

      10031151374

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] William Harvey Lecture: Importance of coronary vasomotion abnormalities –From bench to bedside-2014

    • Author(s)
      Shimokawa H.
    • Organizer
      European Society Congress 2014
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Asian Lecture in Vascular Biology: Light and dark of reactive oxygen species for vascular function.2014

    • Author(s)
      Shimokawa H.
    • Organizer
      Pharmacology & Pgysiology International Scientific Congress 2014/Asian Society of Vascular Bilogy Meeting
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Year and Date
      2014-08-22 – 2014-08-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Symposium: Coronary vasospasm: what do we know and why is it important?: Pathogenesis of vasospastic angina.2014

    • Author(s)
      Shimokawa H.
    • Organizer
      2014 World Congress of Cardiology
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2014-05-04 – 2014-05-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] 「循環器内科」特集/循環器疾患と分子遺伝学 肺高血圧症の分子基盤2015

    • Author(s)
      佐藤 公雄、下川 宏明.
    • Total Pages
      8
    • Publisher
      科学評論社
    • Related Report
      2014 Annual Research Report
  • [Book] 『酸化ストレスの医学 改訂第2版』(2014年8月) 心疾患と酸化ストレス2014

    • Author(s)
      佐藤 公雄、下川 宏明.
    • Total Pages
      7
    • Publisher
      診断と治療社
    • Related Report
      2014 Annual Research Report
  • [Book] 日本医師会雑誌 1412013

    • Author(s)
      下川宏明
    • Publisher
      日本医師会
    • Related Report
      2013 Research-status Report
  • [Remarks] 東北大学循環器内科

    • URL

      http://www.cardio.med.tohoku.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] サイクロフィリンAによる心血管疾患の検査方法2014

    • Inventor(s)
      下川宏明、佐藤公雄 (国立大学法人東北大学)
    • Industrial Property Rights Holder
      下川宏明、佐藤公雄 (国立大学法人東北大学)
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-239615
    • Filing Date
      2014-10-30
    • Acquisition Date
      2015-02-10
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] サイクロフィリンAによる心血管疾患の検査方法2013

    • Inventor(s)
      下川宏明、佐藤公雄 (国立大学法人東北大学)
    • Industrial Property Rights Holder
      下川宏明、佐藤公雄 (国立大学法人東北大学)
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-10-29
    • Acquisition Date
      2015-02-10
    • Related Report
      2014 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 「サイクロフィリンAによる心血管疾患の検査方法」2013

    • Inventor(s)
      下川宏明、佐藤公雄 (国立大学法人東北大学)
    • Industrial Property Rights Holder
      東北大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-10-29
    • Related Report
      2013 Research-status Report
    • Overseas

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi