Basic Research on the Treatment of Cardiovasular Disease by Regulating Aging Signals

• Project/Area Number: 21390237
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Chiba University
• Principal Investigator: MINAMINO Tohru 千葉大学, 大学院・医学研究院, 講師 (90328063)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2009: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
• Keywords: 分子心臓病態学 / 老化 / 心不全 / p53 / 炎症 / インスリン抵抗性 / 脂肪組織 / インスリン / 血管新生

Research Abstract

he incidence and the prevalence of diabetes, heart failure, coronary heart disease and hypertension increase with advancing age. However, the molecular mechanisms underlying the increased risk of such diseases that is conferred by aging remain unclear. In the present study, we demonstrated that cellular aging signals contribute to the pathogenesis of cardiovascular disease.

Research Products

• [Journal Article] Agonist-independent constitutive activity of angiotensin II receptor promotes cardiac remodeling in mice (2012)
  • Author(s): Yasuda N, Akazawa H, Ito K, Shimizu I, Kudo-Sakamoto Y, Yabumoto C, Yano M, Yamamoto R, Ozasa Y, Minamino T, Naito AT, Oka T, Shiojima I, Tamura K, Umemura S, Nemer M, Komuro I
  • Journal Title: Hypertension Volume: 59 Issue: 3 Pages: 627-633
  • DOI: 10.1161/hypertensionaha.111.175208
  • Peer Reviewed
• [Journal Article] p53-induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure (2012)
  • Author(s): Shimizu I, Yoshida Y, Katsuno T, Tateno K, Okada S, Moriya J, Yokoyama M, Nojima A, Ito T, Zechner R, Komuro I, Kobayashi Y, Minamino T
  • Journal Title: Cell Metab Volume: 15 Issue: 1 Pages: 51-64
  • DOI: 10.1016/j.cmet.2011.12.006
  • Peer Reviewed
• [Journal Article] Aldosterone Does Not Contribute to Renal p21 Expression During the Development of Angiotensin II-Induced Hypertension in Mice (2012)
  • Author(s): Nakano D, Minamino T, et al
  • Journal Title: Am J Hypertens Volume: 25 Issue: 3 Pages: 354-358
  • DOI: 10.1038/ajh.2011.224
  • Peer Reviewed
• [Journal Article] Role of JAGGED1 in arterial lesions after vascular injury (2011)
  • Author(s): Wu X, Zou Y, Zhou Q, Huang L, Gong H, Sun A, Tateno K, Katsube K, Radtke F, Ge J, Minamino T, Komuro I
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 31 Pages: 2000-2006
  • Peer Reviewed
• [Journal Article] 心不全と炎症 (2011)
  • Author(s): 南野徹
  • Journal Title: 日本薬理学会雑誌 Volume: 138 Issue: 6 Pages: 187-191
  • DOI: 10.1161/atvbaha.109.185694
• [Journal Article] 脂肪老化とインスリン抵抗性 (2011)
  • Author(s): 南野徹
  • Journal Title: 日本老年医学会雑誌 Volume: 48 Pages: 123-126
  • NAID: 10030469312
• [Journal Article] In vivo tracking of transplanted mononuclear cells using manganese-enhanced magnetic resonance imaging (2011)
  • Author(s): Odaka K, Minamino T, et al
  • Journal Title: PLos One Volume: 6 Issue: 10 Pages: e25487-e25487
  • DOI: 10.1371/journal.pone.0025487
  • Peer Reviewed
• [Journal Article] Ca2+/calmodulin-dependent kinase IIdelta causes heart failure by accumulation of p53 in dilated cardiomyopathy (2010)
  • Author(s): Toko H, Takahashi H, Kayama Y, Oka T, Minamino T, Okada S, Morimoto S, Zhan DY, Terasaki F, Anderson ME, Inoue M, Yao A, Nagai R, Kitaura Y, Sasaguri T, Komuro I
  • Journal Title: Circulation Volume: 122 Pages: 891-899
  • Peer Reviewed
• [Journal Article] ATF6 is important under both pathological and physiological states in the heart (2010)
  • Author(s): Toko H, Takahashi H, Kayama Y, Okada S, Minamino T, Terasaki F, Kitaura Y, Komuro I
  • Journal Title: J. Mol. Cell Cardiol Volume: 49 Issue: 9 Pages: 113-20
  • DOI: 10.1161/circulationaha.109.935296
  • Peer Reviewed
• [Journal Article] Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury (2010)
  • Author(s): Naito AT, Okada S, Minamino T, Iwanaga K, Liu M, Sumida T, Nomura S, Sahara N, Mizoroki T, Takashima A, Akazawa H, Nagai T, Shiojima I, Komuro I
  • Journal Title: Circ Res Volume: 106 Issue: 1 Pages: 1692-1702
  • DOI: 10.1016/j.yjmcc.2010.03.020
  • Peer Reviewed
• [Journal Article] Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury (2010)
  • Author(s): Naito AT, Okada S, Minamino T, Iwanaga K, Liu ML, Sumida T, Nomura S, Sahara N, Mizoroki T, Takashima A, Akazawa H, Nagai T, Shiojima I, Komuro I
  • Journal Title: Circ Res Volume: 106 Issue: 11 Pages: 1692-1702
  • DOI: 10.1161/circresaha.109.214346
  • Peer Reviewed
• [Journal Article] Inhibition of semaphorin as a novel strategy for therapeutic angiogenesis (2010)
  • Author(s): Moriya J, Minamino T, Tateno K, Okada S, Uemura A, Shimizu I, Yokoyama M, Nojima A, Okada M, Koga H, Komuro I
  • Journal Title: Circ. Res Volume: 106 Issue: 5 Pages: 391-398
  • DOI: 10.1172/jci40096
  • Peer Reviewed
• [Journal Article] 老化と酸化ストレス (2010)
  • Author(s): 小笠原陽子, 南野徹
  • Journal Title: Heart View Volume: 14 Pages: 74-78
• [Journal Article] 心血管老化のメカニズム (2010)
  • Author(s): 南野徹
  • Journal Title: 循環器専門医 Volume: 18 Pages: 11-17
• [Journal Article] 老化分子としてのp53と生活習慣病 (2010)
  • Author(s): 南野徹
  • Journal Title: 実験医学 Volume: 28 Pages: 383-389
• [Journal Article] Ca2+/calmodulin-dependent kinase IIdelta causes heart failure by accum ulation of p53 in dilated cardiomyopathy (2010)
  • Author(s): Toko H, Minamino T, et al
  • Journal Title: Circulation Volume: 122 Pages: 891-899
  • Peer Reviewed
• [Journal Article] ATF6 is important under both pathological and physiological states in the heart (2010)
  • Author(s): Toko H, Minamino T, et al
  • Journal Title: J Mol Cell Cardiol Volume: 49 Pages: 113-120
  • Peer Reviewed
• [Journal Article] Role of cellular senescence in lifestyle-related disease (2010)
  • Author(s): Minamino T
  • Journal Title: Circ J Volume: 74 Pages: 2527-2533
  • NAID: 10027423858
  • Peer Reviewed
• [Journal Article] Inhibition of semaphorin as a novel strategy for therapeutic angiogenesis (2010)
  • Author(s): Moriya J, Minamino T, et al
  • Journal Title: Circ Res 106 Pages: 391-398
  • Peer Reviewed
• [Journal Article] A crucial role for adipose tissue p53 in the regulation of insulin resistance (2009)
  • Author(s): Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, Ito T, Nojima A, Nabetani A, Oike Y, Matsubara H, Ishikawa F, Komuro I
  • Journal Title: Nat. Med Volume: 15 Issue: 2 Pages: 1082-1087
  • DOI: 10.1161/circresaha.109.210815
  • Peer Reviewed
• [Journal Article] Cardiac 12/15-lipoxygenase-induced inflammation is involved in heart failure (2009)
  • Author(s): Kayama Y, Minamino T, Toko H, Sakamoto M, Shimizu I, Takahashi H, Okada S, Tateno K, Moriya J, Yokoyama M, Nojima A, Yoshimura M, Egashira K, Aburatani H Komuro I
  • Journal Title: J. Exp. Med Volume: 206 Issue: 9 Pages: 1565-1574
  • DOI: 10.1038/nm.2014
  • Peer Reviewed
• [Journal Article] Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia (2009)
  • Author(s): Moriya J, Minamino T, Tateno K, Shimizu N, Kuwabara Y, Sato Y, Saito Y Komuro I
  • Journal Title: Circ Cardiovasc Interven Volume: 2 Issue: 7 Pages: 245-254
  • DOI: 10.1084/jem.20082596
  • Peer Reviewed
• [Journal Article] Protective role of SIRT1 in diabetic vascular dysfunction (2009)
  • Author(s): Orimo M, Minamino T, Miyauchi H, Tateno K, Okada S, Moriya J, Komuro I
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 29 Issue: 3 Pages: 889-894
  • DOI: 10.1161/circinterventions.108.799361
  • Peer Reviewed
• [Journal Article] アンジオテンシンII.高血圧(上)第4版日本における最新の研究動向 (2009)
  • Author(s): 南野徹
  • Journal Title: 日本臨床 Volume: 67 Pages: 179-183
• [Journal Article] A crucial role for adipose tissue p53 in the regulation of insulin resistance (2009)
  • Author(s): Minamino T, et al
  • Journal Title: Nat Med 15 Pages: 1082-1087
  • Peer Reviewed
• [Journal Article] Cardiac 12/15-lipoxygenase-induced inflammation is involved in heart failure (2009)
  • Author(s): Kayama Y, Minamino T, et al
  • Journal Title: J Exp Med 206 Pages: 1565-1574
  • Peer Reviewed
• [Journal Article] Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia (2009)
  • Author(s): Moriya J, Minamino T, et al
  • Journal Title: Circ Cardiovasc Intervent 2 Pages: 245-254
  • Peer Reviewed
• [Journal Article] Protective role of SIRT1 in diabetic vascular dysfunction (2009)
  • Author(s): Orimo M, Minamino T, et al
  • Journal Title: Arterioscler Thromb Vasc Biol 29 Pages: 889-894
  • Peer Reviewed
• [Journal Article] Gap junctions mediate the spread of ischemia-reperfusion injury (2009)
  • Author(s): Minamino T
  • Journal Title: Circ J 73 Pages: 1591-1592
  • NAID: 10025934585
  • Peer Reviewed
• [Presentation] Lifespan regulatory system and cardiovascular disease (2012)
  • Author(s): Minamino T
  • Organizer: 第76回日本循環器学会・学術集会
  • Place of Presentation: Topics福岡
• [Presentation] Lifestyle-related disease and cellular aging signal network (2011)
  • Author(s): 南野徹
  • Organizer: 日本血管生物医学会
  • Place of Presentation: 京都
  • Year and Date: 2011-12-01
• [Presentation] 細胞老化シグナルによる寿命制御と加齢関連疾患 (2011)
  • Author(s): 南野徹
  • Organizer: 第84回日本内分泌学会 教育講演
  • Place of Presentation: 神戸(招待講演)
  • Year and Date: 2011-04-22
• [Presentation] Molecular mechanism of cardiovascular aging and regeneration (2010)
  • Author(s): Minamino T
  • Organizer: 日本循環器学会総会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-06
• [Presentation] Cellular aging and lifestyle-related disease (2010)
  • Author(s): Minamino T
  • Organizer: 7th Japanese-German Frontiers of Science Symposium Potsdam
  • Place of Presentation: Germany
• [Presentation] Aging signals involved in glucose homeostasis JST Danish-Japanese Workshop "Molecular Diabetology" Copenhagen (2010)
  • Author(s): Minamino T
  • Place of Presentation: Denmark
• [Presentation] Vascular aging and vascular injury : synonymous or analogous? (2010)
  • Author(s): Minamino T
  • Organizer: 20th World Congress of the International Society of Heart Research
• [Book] Annual Review糖尿病・代謝・内分泌2011 (2011)
  • Author(s): 横山真隆, 南野徹
  • Publisher: 中外医学社
• [Book] Annual Review循環器2011 (2011)
  • Author(s): 森谷純治, 南野徹
  • Publisher: 中外医学社
• [Book] 老年医学Update 2010-2011 (2010)
  • Author(s): 南野徹
  • Publisher: メジカルビュー社(印刷中)
• [Book] II.疾患の病因と病態,1.p53と生活習慣病,Annual Review循環器2011,山口徹編
  • Author(s): 森谷純治, 南野徹
  • Publisher: 中外医学社
• [Patent(Industrial Property Rights)] 抗ノッチ1アゴニスト抗体を含む組織再生治療剤及び該抗体を使用する組織再生治療方法 (2012)
  • Inventor(s): 南野徹, 舘野馨, 八木田秀雄
  • Industrial Property Rights Holder: 千葉大学
  • Patent Publication Number: 2012-056934
  • Acquisition Date: 2012-03-22
• [Patent(Industrial Property Rights)] 糖尿病の治療剤 (2010)
  • Inventor(s): 南野徹, 森谷純治
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 2010-232400
  • Filing Date: 2010-10-15