Molecular Mechanisms of Hyper-contraction of Drug-eluting Stent Implanted Coronary Arteries

• Project/Area Number: 20590875
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tohoku University
• Principal Investigator: YASUDA Satoshi Tohoku University, 大学院・医学系研究科, 准教授 (00431578)
• Co-Investigator(Kenkyū-buntansha): SHIMOKAWA Hiroaki 東北大学, 大学院・医学系研究科, 教授 (00235681)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 循環器・高血圧 / トランスレーショナルリサーチ / 冠動脈スラント / Rho-kinase / 血管平滑筋 / 炎症 / 血栓 / カルシウム拮抗薬 / 冠動脈ステント / 血管反応性

Research Abstract

Accumulating evidence indicates that coronary vasoconstricting responses are enhanced at the edges of coronary segment implanted with drug-eluting stents (DES) compared with bare-metal stent (BMS) in humans. We have recently demonstrated that Rho-kinase pathway plays an important role in DES-induced coronary hyperconstricting responses in pigs in vivo and in patients with coronary artery diseases. Also, chronic treatment with long-acting nifedipine suppresses DES-induced coronary hyperconstricting responses and inflammatory changes, at least in part, through Rho-kinase pathway inhibition in pigs in vivo.

Research Products

• [Journal Article] Treatment with nifedipine suppresses coronary hyperconstricting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo-Possible involvement of Rho-kinase pathway- (2011)
  • 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. in press
  • Peer Reviewed
• [Journal Article] Enhanced Rho-kinase activity in circulating neutrophils of patients with vasospastic angina. (2011)
  • Author(s): Kikuchi Y, Yasuda S, Aiazawa K, Tsuburaya R, Ito Y, Takeda M, Nakayama M, Ito K, Takahashi J, Shimokawa H.
  • Journal Title: -possible biomarker for diagnosis and disease activity assessment-J Am Coll Cardiol. in press
  • Peer Reviewed
• [Journal Article] Long-Term Treatment with Eicosapentaenoic Acid Ameliorates Myocardial Ischemia-Reperfusion Injury in Pigs in Vivo-Involvement of Rho-kinase Pathway Inhibition-. (2011)
  • Author(s): Gao JY, Yasuda S, Tsuburaya R, Ito Y, Shiroto T, Hao K, Aizawa K, Kikuchi Y, Ito K, Shimokawa H.
  • Journal Title: Circ J. in press
  • NAID: 10029127641
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid reduces ischemic ventricular fibrillation via altering monophasic action potential in pigs. (2011)
  • Author(s): Tsuburaya R, Yasuda S, Ito Y, Shiroto T, Gao YJ, Ito K, Shimokawa H.
  • Journal Title: J Moll Cell Cardiol. in press
  • Peer Reviewed
• [Journal Article] Treatment with nifedipine suppresses coronary hyperconstricting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo -Possible involvement of Rho-kinase pathway- (2011)
  • Author(s): Tsuburaya R, Yasuda S, et al.
  • Journal Title: Eur Heart J. Volume: 未定(In press)
  • Peer Reviewed
• [Journal Article] Authors' reply. (2010)
  • Author(s): Yasuda S, Shiroto T, Shimokawa H.
  • Journal Title: J Am Coll Cardiol. 55 Pages: 1399-1400
  • Peer Reviewed
• [Journal Article] Authors' reply. (2010)
  • Author(s): Yasuda S, Shiroto T, Shimokawa H
  • Journal Title: J Am Coll Cardiol. Volume: 55 Pages: 1399-1400
  • Peer Reviewed
• [Journal Article] Reply (2010)
  • Author(s): Yasuda S, Shiroto T, Shimokawa H.
  • Journal Title: J Am Coll Cardiol. (In press)
  • Peer Reviewed
• [Journal Article] Role of Rho-kinase in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stent in pigs in vivo. (2009)
  • Author(s): Shiroto T, Yasuda S, Tsuburaya R, Ito Y, Takahashi J, Ito K, Ishibashi-Ueda H, Shimokawa H.
  • Journal Title: J Am Coll Cardiol. 54 Pages: 2321-2329
  • Peer Reviewed
• [Journal Article] Role of Rho-kinase in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stent in pigs in vivo. (2009)
  • Author(s): Shiroto T, Yasuda S, et al.
  • Journal Title: J Am Coll Cardiol. Volume: 54 Pages: 2321-2329
  • Peer Reviewed
• [Journal Article] Role of Rho-kinase in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stents in pigs in vivo. (2009)
  • Author(s): Shiroto T, Yasuda S, Tsuburaya R, Ito Y, Takahashi J, Ito K, Ishibashi-Ueda H, Shimokawa H.
  • Journal Title: J Am Coll Cardiol. 54(24) Pages: 2321-2329
  • Peer Reviewed
• [Presentation] Involvement of Rho-kinase Activation in the Pathogenesis of coronary hyperconstricting responses by drug-eluting stents in patients with coronary artery disease. (2011)
  • Author(s): Aizawa K, Yasuda S, Takahashi J, Takii T, Kikuchi Y, Tsuburaya R, Ito Y, Ito K, Nakayama M, Takeda M, Shimokawa H.
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Long-term treatment with nifedipine suppresses coronary hyperconstricting responses induced by paclitaxel-eluting stent in pigs in vivo -Possible involvement of Rho-kinase. (2011)
  • Author(s): Tuburaya R, Yasuda S, Aizawa K, Gao JY, Ito Y, Shiroto T, Ito K, Ishibashi-Ueda H, Shimokawa H.
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Rho-kinase activity in circulating neutrophils for diagnosis and disease activity assessment of vasospastic angina. (2011)
  • Author(s): Kikuchi Y, Aizawa K, Yasuda S, Tsuburaya R, Ito Y, Matsumoto Y, Takeda M, Nakayama M, Ito K, Takahashi J, Shimokawa H.
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Long-term treatment with eicosapentaenoic acid ameliorates myocardial ischemia-reperfusion injury in pigs in vivo -Potential involvement of Rho-kinase pathway- (2011)
  • Author(s): Gao JY, Yasuda S, Tsuburaya R, Ito Y, Aizawa K, Kikuchi Y, Ito K, Shimokawa H.
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Long-term treatment with nifedipine suppresses coronary hyperconstricting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo : possible involvement of rho-kinase pathway. (2010)
  • Author(s): Tsuburaya R, Yasuda S, et al.
  • Organizer: Annual Scientific Meeting of the American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-17
• [Presentation] Long-term treatment with nifedipine suppresses coronary hyperconstricting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo : possible involvement of rho-kinase pathway. (2010)
  • Author(s): Tsuburaya R, Yasuda S, Aizawa K, Gao J, Ito Y, Shiroto T, Ito K, Ishibashi-Ueda H, Shimokawa H.
  • Organizer: Annual Scientific Meeting of the American Heart Association
  • Place of Presentation: Chicago, USA.
• [Presentation] Long-term treatment with eicosapentaenoic acid ameliorates myocardial ischemia-reperfusion injury in pigs in vivo -A potential role of Rho-kinase pathway-. (2010)
  • Author(s): Gao JY, Yasuda S, Tsuburaya R, Ito Y, Aizawa K, Kikuchi Y, Ito K, Shimokawa H.
  • Organizer: Annual Scientific Meeting of the American Heart Association;
  • Place of Presentation: Chicago, USA.
• [Presentation] Enhanced Rho-kinase activity in circulating neutrophils in patients with vasospastic angina-Possible usefulness for diagnosis and disease activity assessment-. (2010)
  • Author(s): Kikuchi Y, Aizawa K, Yasuda S, Tsuburaya R, Ito Y, Nakayama M, Takeda M, Ito K, Takahashi J, Shimokawa H.
  • Organizer: Annual Scientific Meeting of the American Heart Association;
  • Place of Presentation: Chicago, USA.
• [Presentation] Rho-kinase pathway plays an important role in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stent. (2009)
  • Author(s): Shiroto T, Yasuda S, Tsuburaya R, Ito Y, Ishibashi-Ueda H, Ito K, Takahashi J, Shimokawa H.
  • Organizer: Annual Scientific Meeting of the American Heart Association;
  • Place of Presentation: Orland, USA
• [Presentation] Rho-kinase pathway plays an important role in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stent. (2009)
  • Author(s): Shiroto T, Yasuda S, Tsuburaya R, Ito Y, Ishibashi-Ueda H, Ito K, Takahashi J, Shimokawa H.
  • Organizer: Annual Scientific Meeting of the American Heart Association
  • Place of Presentation: Orland, USA
• [Presentation] Rho-kinase Pathway Plays an Important Role in the Pathogenesis of Coronary Hyperconstricting Responses Induced by Drug-Eluting Stent (2008)
  • Author(s): Shiroto T, Yasuda S, et.al.
  • Organizer: American Heart Association Scientific Meeting
  • Place of Presentation: New Orleans (USA)
  • Year and Date: 2008-11-10
• [Book] 循環器疾患のサイエンス.東京(冠攣縮性狭心症)(小室一成編) (2010)
  • Author(s): 安田聡, 下川宏明
  • Publisher: 南山堂
• [Book] 冠攣縮性狭心症(小室一成編)(循環器疾患のサイエンス) (2010)
  • Author(s): 安田聡, 下川宏明
  • Total Pages: 236
  • Publisher: 東京:南山堂
• [Book] 冠攣縮性狭心症診療の現状と問題点 (2009)
  • Author(s): 安田聡, 小川久雄, 下川宏明
  • Total Pages: 6
  • Publisher: 日本循環器学会・循環器専門医
• [Remarks] ホームページ等
  • URL: http://www.cardio.med.tohoku.ac.jp/index.html
• [Remarks]
  • URL: http://www.cardia.med.tahoku.ac.jp/index.html
• [Remarks]
  • URL: http://www.cardio.med.tohoku.ac.jp/index.html