Pathophysiological role of TRPV2 as a therapeutic target for cardiomyopathy/heart failure

• Project/Area Number: 20590874
• 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: National Cardiovascular Center Research Institute
• Principal Investigator: IWATA Yuko National Cardiovascular Center Research Institute, 分子生理部, 室長 (80171908)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心筋症 / 心不全 / イオンチャネル / カルシウム / 伸展刺激感受性チャネル / 筋変性 / 筋ジストロフィー / 機能的抗体

Research Abstract

We identified TRPV2 as a principal candidate for Ca^<2+>-entry pathways which result in abnormal Ca^<2+> handling in muscular degeneration caused by cytoskeleton abnormality. Inhibition of endogenous TRPV2 significantly reduced the increase in basal intracellular Ca^<2+> and stretch-induced damage as well as improved muscle function in animal models. These data suggest that enhanced TRPV2 activity is important to trigger muscle damage and that it is a promising therapeutic target for muscular dystrophy and cardiomyopathy.

Research Products

• [Journal Article] Dominant-negative inhibition of Ca^<2+>influx via TRPV2 ameliorates muscular dystrophy in animal models. (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Journal Title: Neuromuscular Disordersea Pages: 20653-20653
• [Journal Article] 筋変性疾患治療に向けたCa^<2+>透過チャネルを標的とした創薬の試み (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Journal Title: 化学工業 61 Pages: 288-293
• [Journal Article] Dominant-negative inhibition of Ca^<2+> influx via TRPV2 ameliorates muscular dystrophy in animal models. (2010)
  • Author(s): Iwata Y., Wakabayashi S.
  • Journal Title: Neuromuscular Disorders Volume: 20 Pages: 653-653
• [Journal Article] 筋変性疾患治療に向けたCa^<2+>透過チャネルを標的とした創薬の試み (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Journal Title: 化学工業 Volume: 61 Pages: 288-293
• [Journal Article] Essential role of TRPV2 ion channel in the sensitivity of dystrophic muscle to eccentric contractions. (2009)
  • Author(s): Zanou N., Iwata Y., Schakman O., et al
  • Journal Title: FEBS Letters 583 Pages: 3600-3604
  • Peer Reviewed
• [Journal Article] Amelioration of muscular dystrophy by dominant-negative inhibition of Ca^<2+> permeable channel TRPV2 (2009)
  • Author(s): 岩田裕子, et al.
  • Journal Title: Journal of pharmacological science 109 Pages: 96-96
• [Journal Article] Dominant-negative inhibition of Ca^<2+> influx via TRPV2 ameliorates muscular dystrophy in animal models (2009)
  • Author(s): 岩田裕子, et al.
  • Journal Title: Human Molecular Genetics 18 Pages: 824-834
  • Peer Reviewed
• [Journal Article] Dominant-negative inhibition of Ca^<2+> influx via TRPV2 ameliorates muscular dystrophy in animal models. (2009)
  • Author(s): Iwata Y., Katanosaka Y., Arai Y., et al.
  • Journal Title: Hum.Mol.Gen.18:,2009 18 Pages: 824-834
  • Peer Reviewed
• [Journal Article] Dominant-negative inhibition of Ca^<2+> influx via TRPV2 ameliorates muscular dystrophy in animal models (2009)
  • Author(s): Yuko Iwata, et al.
  • Journal Title: Human Molecular Genetics 18 Pages: 824-834
  • Peer Reviewed
• [Journal Article] Amelioration of muscular dystrophy by dominant-negative inhibition of Ca^<2+> permeable channel TRPV2 (2009)
  • Author(s): Yuko Iwata
  • Journal Title: Journal of pharmacological science 109 Pages: 96-96
• [Journal Article] Activation of Na^+/H^+ Exchanger1 is sufficient to generate Ca^<2+> signals that induce cardiac hypertrophy and heart failure (2008)
  • Author(s): 岩田裕子, et al.
  • Journal Title: Circulation Research 103 Pages: 891-899
  • Peer Reviewed
• [Journal Article] Enhanced Na^+/H^+ Exchange activity participates in pathogenesis of muscular dystrophy and cardiomyopathy (2008)
  • Author(s): 岩田裕子, et al.
  • Journal Title: Experimental & Clinical Cardiology 13 Pages: 98-98
• [Journal Article] Activation of Na^+/H^+ exchange is sufficient to induce hypertrophy and heart failure. (2008)
  • Author(s): 岩田裕子, et al.
  • Journal Title: Journal of Molecular and Cellular Cardiology 45S17
• [Journal Article] Activation of Na^+/H^+ Exchanger1 is sufficient to generate Ca^<2+> signals that induce cardiac hypertrophy and heart failure (2008)
  • Author(s): Yuko Iwata, et al.
  • Journal Title: Circulation Research 103 Pages: 891-899
  • Peer Reviewed
• [Journal Article] Enhanced Na^+/H^+ Exchange activity participates in pathogenesis of muscular dystrophy and cardiomyopathy (2008)
  • Author(s): Yuko Iwata
  • Journal Title: Experimental & Clinical Cardiology 13 Pages: 98-98
• [Journal Article] Activation of Na^+/H^+ exchange is sufficient to induce hypertrophy and heart failure (2008)
  • Author(s): Yuko Iwata
  • Journal Title: Journal of Molecular and Cellular Cardiology 45
• [Presentation] Ca^<2+>透過チャネルTRPV2の特異的阻害抗体の作成とその筋変性改善効果 (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第83回日本生化学会大会パシフィコ横浜
  • Place of Presentation: 横浜
  • Year and Date: 2010-12-07
• [Presentation] Ca^<2+>-permeable channel TRPV2 as a promising therapeutic target for muscular dystrophy and cardiomyopathy (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第15回世界筋学会
  • Place of Presentation: 熊本市民ホール(熊本)
  • Year and Date: 2010-10-16
• [Presentation] Ca^<2+>-permeable channel TRPV2 as a promising therapeutic for muscular dystrophy and cardiomyopathy (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第15回世界筋学会国際会議(WMS2010)
  • Place of Presentation: 崇城大学市民ホール(熊本)
  • Year and Date: 2010-10-15
• [Presentation] Activation of Ca^<2+>-permeable channel TRPV2 serves as a high risk factor in cardiomyopathy (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第20回国際心臓研究学会(ISHR2010)
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2010-05-16
• [Presentation] 心筋症モデル動物におけるCa^<2+>透過チャネルTRPV2の活性阻害は筋変性を軽減する (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-03-18
• [Presentation] Ca^<2+>透過チャネルTRPV2の特異的阻害抗体の作成とその筋変性改善効果 (2010)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(横浜)
• [Presentation] 拡張型心筋症発症におけるCa^<2+>透過チャネルTRPV2の病態的役割 (2009)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2009-10-24
• [Presentation] Amerioration of muscular dystrophy by dominant-negative inhibition of Ca2+ influx via (2009)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: TRPV2国際生理学会IUPS2009
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2009-07-30
• [Presentation] Amerioration of muscular dystrophy by dominant-negative inhibition of Ca^<2+> influx via TRPV2 (2009)
  • Author(s): 岩田裕子
  • Organizer: 国際生理学会IUPS2009
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2009-07-30
• [Presentation] Ca^<2+>-permeable channel TRPV2 as a promising therapeutic targetfor muscular dystrophy (2009)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第8回日仏ワークショップパリ
  • Place of Presentation: ミオロジー研究所(フランス)
  • Year and Date: 2009-07-03
• [Presentation] Ca^<2+>-permeable channel TRPV2 as a promising therapeutic target for muscular dystrophy (2009)
  • Author(s): 岩田裕子
  • Organizer: 第8回日仏ワークショップ
  • Place of Presentation: パリ ミオロジー研究所(フランス)
  • Year and Date: 2009-07-03
• [Presentation] Ca^<2+>透過チャネルTRPV2阻害による筋変性疾患病態改善効果 (2009)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 生理研研究会「TRPチャネル群の生理機能と病態生理」
  • Place of Presentation: 岡崎カンファレンスセンター(岡崎)
  • Year and Date: 2009-06-04
• [Presentation] Ca^<2+>透過チャネルTRPV2阻害による筋変性疾患態改善効果 (2009)
  • Author(s): 岩田裕子
  • Organizer: 生理研研究会「TRPチャネル群の生理機能と病態生理」
  • Place of Presentation: 岡崎カンファレンスセンター(岡崎)
  • Year and Date: 2009-06-04
• [Presentation] Ca^<2+>透過チャネルTRPV2のドミナントネガティブ阻害による筋ジストロフィー病態改善効果 (2009)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-03-17
• [Presentation] Ca^<2+>透過チャネルTRPV2のドミナントネガティブ変異体による筋ジストロフィーの病態改善効果 (2008)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-10
• [Presentation] Activation of Na^+/H^+ exchange is sufficient to induce hypertrophy and heart failure (2008)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 第25回国際心臓研究学会(ISHR)日本部会
  • Place of Presentation: 横浜開港記念会館
  • Year and Date: 2008-12-05
• [Presentation] Enhanced Na^+/H^+ Exchange Activity participates in pathogenesis of muscular dystrophy and cardiomyopathy (2008)
  • Author(s): 岩田裕子, 若林繁夫
  • Organizer: 心筋代謝研究会
  • Place of Presentation: 東京慈恵会医科大学
  • Year and Date: 2008-07-13
• [Presentation] Enhanced Na^+/H^+ Exchange Activity participates in pathogenes is of muscular dystrophy and cardiomyopathy (2008)
  • Author(s): Yuko Iwata, et al
  • Organizer: 心筋代謝研究会
  • Place of Presentation: 東京慈恵会医科大学
  • Year and Date: 2008-07-13
• [Remarks] ホームページ等
  • URL: http://www.ncvc.go.jp/res/bunshi/bunshij.html
• [Remarks]
  • URL: http://www.ncvc.go.jp/res/bunshi/bunshij.html
• [Patent(Industrial Property Rights)] 抗TRPV2抗体 (2010)
  • Inventor(s): 岩田裕子、若林繁夫
  • Industrial Property Rights Holder: 国立循環器病センター
  • Industrial Property Number: 2010-016760
  • Filing Date: 2010-01-28
• [Patent(Industrial Property Rights)] 抗TRPV2抗体 (2010)
  • Inventor(s): 岩田裕子, 若林繁夫
  • Industrial Property Rights Holder: 国立循環器病センター
  • Industrial Property Number: 2010-016760
  • Filing Date: 2010-01-28
• [Patent(Industrial Property Rights)] TRPV2の部分ペプチド (2009)
  • Inventor(s): 岩田裕子、若林繁夫
  • Industrial Property Rights Holder: 国立循環器病センター
  • Industrial Property Number: 2009-186219
  • Filing Date: 2009-08-11