The role of SmgGDS in the pleiotropic effects by statins

• Project/Area Number: 23659071
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: SHIMOKAWA Hiroaki 東北大学, 大学院・医学系研究科, 教授 (00235681)
• Co-Investigator(Kenkyū-buntansha): SATOH Kimio 東北大学, 高等教育開発推進センター, 准教授 (80436120)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: シグナル伝達 / スタチン / 低分子量G蛋白

Research Abstract

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 by3-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.

Research Products

• [Journal Article] Statins exert pleiotropic effects through SmgGD S up-regulation with a resultant Rac l degradation (2013)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Plasma Cyclophilin A Is a Novel Biomarker for Coronary Artery Disease (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Statins exert pleiotropic effects through SmgGDS up-regulation with a resultant Rac1 degradation. (2013)
  • Author(s): Tanaka S
  • Journal Title: Arterioscler Throm Vasc Biol. Volume: 33
  • Peer Reviewed
• [Journal Article] Essential role of the bone marrow for microvascular endothelial and metabolic functions in mice (2012)
  • Author(s): Nakaj ima S, Ohashi J, Sawada A, Noda K, Fukumoto Y, Shimokawa H
  • Journal Title: Circ Res Volume: 111 Issue: 1 Pages: 87-96
  • DOI: 10.1161/circresaha.112.270215
  • Peer Reviewed
• [Journal Article] Mechanisms for Enhanced Endothelium-Derived Hyperpolarizing Factor-Mediated Responses in Microvessels in Mice (2012)
  • Author(s): Ohashi J, Sawada A, Nakjiima S, Noda K, Takaki A, Shimokawa H
  • Journal Title: Circulation Journal Volume: 76 Issue: 7 Pages: 1768-1779
  • DOI: 10.1253/circj.CJ-12-0197
  • NAID: 10030503846
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Long-term treatment with nifedipine suppresses coronary hyperconstrcting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo: Possible involvement of Rho-kinase pathway- (2012)
  • Author(s): Tsuburaya R, Yasuda S, Shiroto T, Ito Y, Gao JY, Aizawa K, Kikuchi Y, Ito K, Takahashi J, Ishibashi-Ueda H, Shimokawa H.
  • Journal Title: Eur Heart J Volume: 33 Issue: 6 Pages: 791-799
  • DOI: 10.1093/eurheartj/ehr145
  • Peer Reviewed
• [Journal Article] The Great East Japan Earthquake Disaster and cardiovascular diseases (2012)
  • Author(s): Tatsuo Aoki
  • Journal Title: Eur Heart J. Volume: 33 Issue: 22 Pages: 2796
  • DOI: 10.1093/eurheartj/ehs288
  • Peer Reviewed
• [Journal Article] Emergence of the erythropoietin/erythropoietin receptor system as a novel cardiovascular target (Review). (2012)
  • Author(s): Kimio Satoh
  • Journal Title: J Cardiovasc Pharmacol. Volume: 58 Issue: 6 Pages: 570-574
  • DOI: 10.1097/fjc.0b013e318235e7bb
  • Peer Reviewed
• [Journal Article] Mechanisms for enhanced endothelium-derived hyperpolarizing factor-medited responses in microvessels in mice. (2012)
  • Author(s): Ohashi J, Sawada A, Shimokawa H, et al.
  • Journal Title: Circulation Journal Volume: in press
  • Peer Reviewed
• [Journal Article] Vascular-derived reactive oxygen species for homeostasis and diseases (2011)
  • Author(s): Satoh K, Shimokawa H
  • Journal Title: Nitric Oxide Volume: 25 Issue: 2 Pages: 211-215
  • DOI: 10.1016/j.niox.2011.04.005
  • Peer Reviewed
• [Journal Article] Rho-kinase:Important new therapeutic target in cardiovascular diseases (2011)
  • Author(s): Satoh K, Fukumoto Y, Shimokawa H
  • Journal Title: Am J Physiol Volume: 301 Issue: 2 Pages: 287-296
  • DOI: 10.1152/ajpheart.00327.2011
  • Peer Reviewed
• [Journal Article] Eocosapentaenoic acid reduces ischemic ventricular fibrillation via altering monophasic action potentials. (2011)
  • Author(s): Tsuburaya R, Yasuda S, Shimokawa H, et al.
  • Journal Title: European Heart Journal. Volume: 51 Pages: 329-336
  • Peer Reviewed
• [Presentation] Recent progress in endothelial research (2013)
  • Author(s): Shimokawa H
  • Organizer: Invited lecture at Royal Adelaide Hospital
  • Place of Presentation: Adelaide, Australia
  • Year and Date: 2013-04-30
• [Presentation] Update on coronary spasm (2013)
  • Author(s): Shimokawa H
  • Organizer: Rome Cardiology Forum 2012
  • Place of Presentation: Rome, Italy
  • Year and Date: 2013-03-30
• [Presentation] Rho-kinase as an important new therapeutic target in cardiovascular medicine (2013)
  • Author(s): Shimokawa H.
  • Organizer: Invited lecture at the San Raffaele University
  • Place of Presentation: Milano, Italy
  • Year and Date: 2013-03-30
• [Presentation] Role of Rho/Rho-kinase pathway in the cardiovascular system (2012)
  • Author(s): Shimokawa H.
  • Organizer: 6th European Congress of Pharmacology
  • Place of Presentation: Granada, Spain
  • Year and Date: 2012-07-19
• [Presentation] Present status & future perspectives of heart failure in Japan (2012)
  • Author(s): Shimokawa H.
  • Organizer: Invited lecture at the Flinders Medical Center
  • Place of Presentation: Adelaide, Australia
  • Year and Date: 2012-05-02
• [Presentation] Coronary spasm in 2012: Mechanisms and treatment (2012)
  • Author(s): Shimokawa H
  • Organizer: Invited lecture at the Cardiac Society of Australia & New Zealand Meeting
  • Place of Presentation: Adelaide, Australia
  • Year and Date: 2012-05-01
• [Presentation] Rho-kinase as an important CV therapeutic target (2012)
  • Author(s): Shimokawa H
  • Organizer: Invited lecture at Medical Grand Round of the Queen Elizabeth Hospital
  • Place of Presentation: Adelaide, Australia
  • Year and Date: 2012-05-01
• [Presentation] Recent progress in endothelial research (2012)
  • Author(s): Shimokawa H
  • Organizer: Invited lecture at the Cardiology Academic Meeting of the Queen Elizabeth Hospital
  • Place of Presentation: Adelaide, Australia
  • Year and Date: 2012-05-01
• [Presentation] The Great East Japan Earthquake Disaster and cardiovascular diseases (2012)
  • Author(s): Shimokawa H
  • Organizer: European Society of Cardiology Congress
  • Place of Presentation: Munich, Germany
• [Presentation] Crucial role of SmgGDS in the molecular mechanisms of the pleiotropic effects of HMG-CoA reductase inhibitors. (2011)
  • Author(s): Tanaka S, Nochioka K, Shimokawa H, et al.
  • Organizer: American Heart Association (AHA)
  • Place of Presentation: Orlando, USA
• [Presentation] Symposium: Update on coronary vasomotion
  • Author(s): Hiroaki Shimokawa
  • Organizer: Rome Cardiology Forum 2012
  • Place of Presentation: Rome, Italy
  • Invited
• [Presentation] Coronary spasm in 2012: Mechanisms and treatment.
  • Author(s): Hiroaki Shimokawa
  • Organizer: Invited lecture at the Cardiac Society of Australia & New Zealand Meeting
  • Place of Presentation: Adelaide, Australia
  • Invited
• [Book] 日本人の虚血性心疾患に関する基礎的・臨床的研究 (2013)
  • Author(s): 下川宏明
  • Publisher: 日本医師会雑誌141
• [Book] エリスロポエチンの血管内皮保護作用と血管恒常性維持機構 (2013)
  • Author(s): 佐藤公雄、下川宏明
  • Total Pages: 452
  • Publisher: BIO Clinica.
• [Book] 内皮由来過分極因子の医学的意義.血栓と循環 (2012)
  • Author(s): 下川宏明、神戸茂雄
  • Publisher: メディカルレビュー社
• [Book] 大震災と循環器・呼吸器疾患(序文).呼吸と循環 (2012)
  • Author(s): 下川宏明
  • Publisher: 医学書院
• [Book] H_2O_2が制御する血管弛緩反応 (2012)
  • Author(s): 下川宏明
  • Publisher: 日本薬理学雑誌
• [Book] 肺高血圧診療の進歩をみる.特集にあたって (2012)
  • Author(s): 下川宏明
  • Publisher: Vascular Medicine
• [Book] H2O2が制御する血管弛緩反応. (2012)
  • Author(s): 下川宏明
  • Total Pages: 139
  • Publisher: 日本薬理学雑誌
• [Book] 医学論文の書き方.Circulation Journal編集長からのアドバイス-心臓 (2011)
  • Author(s): 下川宏明
  • Publisher: 日本心臓財団
• [Book] Annual Review 循環器 (2011)
  • Author(s): 福本義弘、下川宏明
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.cardio.med.tohoku.ac.jp/index.html
• [Remarks] 東北大学循環器内科
  • URL: http://www.cardio.med.tohoku.ac.jp/
• [Remarks] なし
• [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 (2012)
  • Inventor(s): 下川宏明、佐藤公雄
  • Industrial Property Rights Holder: 下川宏明、佐藤公雄(国立大学法人東北大学)
  • Industrial Property Number: 2012-239615
  • Filing Date: 2012-10-30
• [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」 (2012)
  • 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: 2012-10-30
• [Patent(Industrial Property Rights)] 「スタチンの用法、用量を決定する方法」 (2012)
  • Inventor(s): 下川宏明、田中眞一（国立大学法人東北大学）
  • Industrial Property Rights Holder: 下川宏明、田中眞一（国立大学法人東北大学）
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2011-197906
  • Filing Date: 2012-09-12
• [Patent(Industrial Property Rights)] 「スタチンの用法、用量を決定する方法」 (2012)
  • Inventor(s): 下川宏明、田中眞一（国立大学法人東北大学）
  • Industrial Property Rights Holder: 下川宏明、田中眞一（国立大学法人東北大学）
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-12-19
  • Overseas
• [Patent(Industrial Property Rights)] スタチンの用法、用量を決定する方法 (2011)
  • Inventor(s): 下川宏明、田中眞一
  • Industrial Property Rights Holder: 下川宏明、田中眞一
  • Industrial Property Number: 2011-197906
  • Filing Date: 2011-09-12
• [Patent(Industrial Property Rights)] スタチンの用法・用量を決定する方法 (2011)
  • Inventor(s): 下川宏明・田中眞一
  • Industrial Property Rights Holder: 下川宏明・田中眞一
  • Filing Date: 2011