Research for the elucidation of the cardiovascular effect and application to treatment by adenosine

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390251
• 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: National Cardiovascular Center Research Institute
• Principal Investigator: KITAKAZE Masafumi 独立行政法人国立循環器病研究センター, 臨床研究部, 部長 (20294069)
• Co-Investigator(Kenkyū-buntansha): ASAKURA Masanori 独立行政法人国立循環器病研究センター, 臨床研究部, 室長 (80443505)
• Co-Investigator(Renkei-kenkyūsha): ASANUMA Hiroshi 京都府立医科大学, 大学院・医学研究科循環器内科学, 准教授 (20416217) ; YAMASAKI Satoru 独立行政法人国立循環器病研究センター, 細胞生物学部, 室長 (70348796)
• Project Period (FY): 2009 – 2011
• Keywords: アデノシン / 心不全診断 / 心不全治療 / トランスレーショナル研究 / 臨床試験

Research Abstract

Adenosine is known to be a key regulatory molecule of cardioprotection. However, it has been difficult to demonstrate the molecular mechanisms for the cardiovascular protective mechanisms of adenosine. To solve this question, we have firstly established the highly-sensitive system of the measurements of plasma adenosine level using LC-MS. Secondly, we demonstrated the multiple cardiovascular protective mechanisms of adenosine in a variety of the pathophysiological condition by the measurement of adenosine levels in the blood and myocardial tissue samples. Moreover, the clarification of the alteration in gene expression levels in patients with heart failure implied that adenosine-related gene expression might modulate the pathophysiology of heart failure, and the addition of adenosine is a candidate for the treatment of heart failure. Fourthly, we showed that the plasma adenosine levels can be a marker of the severity of heart failure in the clinical study. Taken together, we need to focus on the adenosine metabolism in the pathophysiology of cardiovascular diseases via the present study.

Research Products

• [Journal Article] Activation of adenosine A1 receptor attenuates tumor necrosis factor-αinduced hypertrophy of cardiomyocytes (2011)
  • Author(s): Liao Y, Lin L, Lu D, Fu Y, Bin J, Xu D, Kitakaze M
  • Journal Title: Biomed Pharmacother Volume: 65(7) Pages: 491-495
  • Peer Reviewed
• [Journal Article] Isoform-specific intermolecular disulfide bond formation of heterochromatin protein 1(HP1) (2010)
  • Author(s): Higo S, Asano Y, Kato H, Yamazaki S, Nakano A, Tsukamoto O, Seguchi O, Asai M, Asakura M, Asanuma H, Sanada S, Minamino T, Komuro I, Kitakaze M, Takashima S
  • Journal Title: J Biol Chem Volume: 285(41) Pages: 31337-31347
  • Peer Reviewed
• [Journal Article] AMPK controls the speed of microtubule polymerization and directional cell migration via CLIP-170 phosphorylation (2010)
  • Author(s): Nakano A, Watanabe T, Kato H, Min KD, Yamazaki S, Asano Y, Seguchi O, Higo S, Shintani Y, Asanuma H, Asakura M, Minamino T, Kaibuchi K, Mochizuki N, Kitakaze M, Takashima S
  • Journal Title: Nat Cell Biol Volume: 12(6) Pages: 583-590
  • Peer Reviewed
• [Journal Article] Identification of genes related to heart failure using global gene expression profiling of human failing myocardium (2010)
  • Author(s): Min KD, Asakura M, Liao Y, Nakamaru K, Okazaki H, Takahashi T, Fujimoto K, Ito S, Takahashi A, Asanuma H, Yamasaki S, Minamino T, Sanada S, Seguchi O, Nakano A, Ando Y, Otsuka T, Furukawa H, Isomura T, Takashima S, Mochizuki N, Kitakaze M
  • Journal Title: Biochem Biophys Res Commun Volume: 393(1) Pages: 55-60
  • Peer Reviewed
• [Journal Article] Metformin prevents progression of heart failure in dogs : Role of AMP-activated protein kinase (2009)
  • Author(s): Sasaki H, Asanuma H, Fujita M, Takahama H, Wakeno M, Ito S, Ogai A, Asakura M, Kim J, Minamino T, Takashima S, Sanada S, Sugimachi M, Komamura K, Mochizuki N, Kitakaze M
  • Journal Title: Circulation Volume: 119(19) Pages: 2568-2577
  • Peer Reviewed
• [Journal Article] Prolonged targeting of ischemic/reperfused myocardium by liposomal adenosine augments cardioprotection in rats (2009)
  • Author(s): Takahama H, Minamino T, Asanuma H, Fujita M, Asai T, Wakeno M, Sasaki H, Kikuchi H, Hashimoto K, Oku N, Asakura M, Kim J, Takashima S, Komamura K, Sugimachi M, Mochizuki N, Kitakaze M
  • Journal Title: J Am Coll Cardiol Volume: 53(8) Pages: 709-717
  • Peer Reviewed
• [Presentation] Heterogeneity of global gene expression profiles between endocardial and epicardial normal myocardium diminishes in canine failing hearts (2011)
  • Author(s): Min KD, Asakura M, Asanuma H, Ito S, Takahashi A, Sasaki H, Takahama H, Yamazaki S, Mochizuki N, Kitakaze M
  • Year and Date: 20110000
• [Presentation] A novel approach using exon array technique identifies Mtus1 as a new heart failure-related gene (2011)
  • Author(s): Ito S, Asakura M, Min KD, Takahashi A, Yamazaki S, Asanuma H, Mochizuki N, Takashima S, Kitakaze M
  • Year and Date: 20110000
• [Presentation] Effect of Vildagliptin on the improvement of survival in murine pressure-overload heart failure model (2010)
  • Author(s): Takahashi A, Asakura M, Min KD, Ito S, Minamino T, Yan Y, Yamazaki S, Sanada S, Asanuma H, Liao Y, Takashima S, Mochizuki N, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会2010
  • Year and Date: 20100000
• [Book] 冠血流の生理学と虚血カラー版循環器病学 (2010)
  • Author(s): 浅沼博司、北風政史
  • Total Pages: 592-606
  • Publisher: 西村書店
• [Book] 心筋保護を考えた薬剤選択循環器臨床サピア8 (2010)
  • Author(s): 浅沼博司、北風政史
  • Total Pages: 135-137
  • Publisher: 中山書店