脂質沈着による心肥大、心不全進展の病態の解明

• 研究課題/領域番号: 20590859
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 循環器内科学
• 研究機関: 名古屋大学
• 研究代表者: 奥村 健二 名古屋大学, 大学院・医学系研究科, 寄附講座教授 (40262901)
• 研究分担者: 村上 隆一郎 名古屋大学, 医学部附属病院, 助教 (20418742) ; 成 憲武 名古屋大学, 大学院・医学系研究科, 寄附講座講師 (30378228)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円); 2010年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円); 2009年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円); 2008年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
• キーワード: 脂質 / 心肥大 / 心不全 / カルニチン / JVSマウス / Lipids / マトリックスプロテアーゼ / Remodeling / Atherocsclerosis / Neovascularization / Cardiac hypertrophy / Heart Failure / アディポネクチン / 血管内皮機能

研究概要

遺伝子異常によって特異的な心肥大を呈するjuvenile visceral steatosis(JVS)マウスではカルニチン欠乏のための脂肪酸代謝の異常がイノシトール脂質や1,2-ジアシルグリセロールを始めとする脂質系細胞情報伝達物質を変化させシグナル伝達機構の障害をもたらしている可能性を示した。また、ヘテロ体ではほとんど機能障害がなく生命予後もWild-typeマウスと同じと考えられていたが、JVSマウスのヘテロ体に圧を負荷することにより心肥大を示し、心不全によって寿命が短くなった。このように、脂質代謝の異常が心不全に関与することが示された。

研究成果

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  • 雑誌名: J Am Coll Cardiol. 53 ページ: 1040-1046
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• [雑誌論文] Mesenchymal stem cell-based gene therapy with prostacyclin synthase enhanced neovascularization in hindlimb ischemia. (2009)
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• [雑誌論文] Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats. (2009)
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• [雑誌論文] Microsomal triglyceride transfer protein gene polymorphism strongly influences circulating malondialdehyde-modified low-density lipoprotein. (2009)
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• [雑誌論文] Mechanism of diastolic stiffening of the failing myocardium and its prevention by angiotensin receptor and calcium channel blockers. (2009)
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• [雑誌論文] Mechanism of diastolic stiffening of the failing myocardium and its prevention by angiotensin receptor and calcium channel blockers. (2009)
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• [雑誌論文] Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats. (2009)
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• [雑誌論文] Mesenchymal stem cell-based gene therapy with prostacyclin synthaseenhanced neovascularization in hindlimb ischemia. (2009)
  • 著者名/発表者名: Ishii M, Okumura K, Murakami R., et al.
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• [雑誌論文] Circulating malondialdehyde-modified low-density lipoprotein is strongly associated with very small low-density lipoprotein cholesterol concentrations in healthy men (2009)
  • 著者名/発表者名: Takahashi R, Cheng XW, Okumura K, et al
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  • 査読あり
• [雑誌論文] Microsomal triglyceride transfer protein gene polymorphism strongly influences circulating malondialdehyde-modified low-density lipoprotein (2009)
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• [学会発表] Statin prevents apoptosis in response to oxidative stress and inflammation in atherogenic plaque via enhancement of antiapoptotic protein IAP-2 and Bcl-2 associated with activation of eNOs : implication for plaque stability. (2009)
  • 著者名/発表者名: 成憲武、葛谷雅文、宋海珍、胡莉ナ、佐々木健、井上愛子、中村香江、奥村健二、室原豊明
  • 学会等名: 第17回日本血管生物医学会学術集会
  • 発表場所: 東京
  • 年月日: 2009-12-03
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  • 年月日: 2009-11-09
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  • 学会等名: Scientific Sections.
  • 発表場所: New Orleans, Louisiana, USA.
  • 年月日: 2008-11-11
• [学会発表] Statin prevents apoptosis in response to oxidative stress in atherogenic plaque via enhancement of antiapoptotic protein IAP-2 : implication for plaque stability. (2008)
  • 著者名/発表者名: Cheng XW, Okumura K, Hu L, Song H, Inoue A, Kuzuya M, Murohara T
  • 学会等名: 5th China-Japan Cardiovascular Forum.
  • 発表場所: Beijing, China.
  • 年月日: 2008-10-23
• [学会発表] Treatment of ApoE-deficient mice with statin inhibits theNADPH oxidase-dependent lysosomal protease cathepsin activation system : implication for plaque stability. (2008)
  • 著者名/発表者名: Cheng XW, Okumura K, Kuzuya M, Inoue A, Song H, Hu L, Murohara T
  • 学会等名: 4^<th>China-Japan Cardiovascular Forum.
  • 発表場所: Beijing, China.
  • 年月日: 2008-10-19
• [学会発表] Very small low-density lipoprotein cholesterol level is a determinant of arterial stiffness in men with impaired glucose metabolism. (2008)
  • 著者名/発表者名: Takahashi R, Okumura K, Yoshikane M, Ikeda N, Murohara T
  • 学会等名: European Society of Cardiology, ESC Congress 2008
  • 発表場所: Munich
  • 年月日: 2008-09-01
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