Translational research of adenosine aiming for diagnosis and treatment of heart failure

2008 Fiscal Year Final Research Report

• Project/Area Number: 19390220
• 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: MASAFUMI Kitakaze National Cardiovascular Center Research Institute, 臨床研究開発部, 部長 (20294069)
• Co-Investigator(Kenkyū-buntansha): ASAKURA Masanori 国立循環器病センター研究所, 心臓血管内科, 医長 (80443505) ; KIM Jiyoong 国立循環器病センター研究所, 臨床研究開発部, 客員研究員 (30393226) ; OGAI Akiko 国立循環器病センター研究所, 疫学部, 室員 (90359274) ; TOMOIKE Hitonobu 国立循環器病センター研究所, 病院, 院長 (90112333)
• Co-Investigator(Renkei-kenkyūsha): TAKASHIMA Seiji 大阪大学, 大学院医学系研究科, 准教授 (90379272) ; MINAMINO Tetsuo 大阪大学, 大学院医学系研究科, 助教授 (30379234) ; NAKATANI Satoshi 大阪大学, 大学院医学系研究科, 教授 (80393221) ; KOMAMURA Kazuo 兵庫医療大学, 薬学部, 教授 (90311448)
• Project Period (FY): 2007 – 2008
• 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

心不全・心臓虚血障害の形成に至る過程に深く関与する生理物質アデノシンに着目し、その病態における役割・治療への応用を検討した。結果、アデノシンが複数あるアデノシン受容体を介して、別個に心不全の病態改善に関与することが明らかになった。さらにアデノシンの心保護作用を臨床応用すべく、心不全患者でのアデノシンおよびその合成酵素量の測定を行い不全心筋での発現上昇を確認し、心臓からのアデノシン産生の重要性を明らかにした。さらにリポゾーム化アデノシンによる心筋虚血障害改善作用を示し、アデノシン産生増強剤とあわせてアデノシンの心不全治療にむけた臨床応用への基盤を確立した。

Research Products

• [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: Journal of the American College of Cardiology 53(8) Pages: 709-717
• [Journal Article] Activation of ecto-5 '-nucleotidase in the blood and hearts of patients with chronic heart failure (2008)
  • Author(s): Fujita M, Asakura M, Sanada S, Funaya H, Tsukamoto O, Komamura K, Asanuma H, Taketani S, Isomura T, Nakamaru K, Furukawa H, Sawa Y, Hori M, Kitakaze M
  • Journal Title: Journal of Cardiac Failure 14(5) Pages: 426-430
• [Journal Article] Long-term oral administration of dipyridamole improves both cardiac and physical status in patients with mild to moderate chronic heart failure: A prospective open-randomized study (2007)
  • Author(s): Sanada S, Asanuma H, Koretsune Y, Watanabe K, Nanto S, Awata N, Hoki N, Fukunami M, Kitakaze M, Hori M
  • Journal Title: Hypertension Research 30(10) Pages: 913-919
• [Journal Article] Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning (2007)
  • Author(s): Fujita M, Asanuma H, Hirata A, Wakeno M, Takahama H, Sasaki H, Kim J, Takashima S, Tsukamoto O, Minamino T, Shinozaki Y, Tomoike H, Hori M, Kitakaze M
  • Journal Title: American Journal of Physiology-Heart and Circulatory Physiology 292(4) Pages: H2004-H2008
• [Journal Article] Impact of adenosine receptor signaling and metabolism on pathophysiology in patients with chronic heart failure (2007)
  • Author(s): Asakura M, Asanuma H, Kim J, Liao Y, Nakamaru K, Fujita M, Komamura K, Isomura T, Furukawa H, Tomoike H, Kitakaze M
  • Journal Title: Hypertension Research 30(9) Pages: 781-787
• [Journal Article] Long-term stimulation of adenosine A2b receptors begun after myocardial infarction prevents cardiac remodeling in rats (2006)
  • Author(s): Wakeno M, Minamino T, Seguchi O, Okazaki H, Tsukamoto O, Okada K, Hirata A, Fujita M, Asanuma H, Kim J, Komamura K, Takashima S, Mochizuki N, Kitakaze M
  • Journal Title: Circulation 114(18) Pages: 1923-1932
• [Journal Article] Catabolism of adenine nucleotides favors adenosine production following exercise in patients with chronic heart failure (2006)
  • Author(s): Kinugawa T, Fujita M, Ogino K, Kato M, Osaki S, Igawa O, Shigemasa C, Hisatome I, Kitakaze M
  • Journal Title: Journal of Cardiac Failure 12(9) Pages: 720-725
• [Presentation] Inhibition of Cardiac Remodeling by Pravastatin is Associated withAmelioration of Endoplasmic Reticulum Stress (2008)
  • Author(s): Zhao H, Liao Y, Minamino T, Asano Y, Asakura M, Kim J, Asanuma H, Takashima S, Hori M, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会 2008
  • Year and Date: 20080000
• [Presentation] Tricuspid E/Ea is a Powerful Predictor of Cardiac Events in Patients with Chronic Pulmonary Hypertension (2008)
  • Author(s): Utsunomiya H, Nakatani S, Okada T, Kanzaki H, Kyotani S, Yamamoto H, Nakanishi N, Kihara Y, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会 2008
  • Year and Date: 20080000
• [Presentation] Histopathological Analysis as Predictive Markers of Recovery from End-Stage Heart Failure in Patients with Left Ventricular Assist Device (2008)
  • Author(s): Takahashi A, Ueda HI, Satake M, Matsuyama TA, Ikeda Y, Yanase M, Kato TS, Kitakaze M, Nakatani T, Tomoike H
  • Organizer: 米国心臓協会年次学術集会 2008
  • Year and Date: 20080000
• [Presentation] Activation of Myocardial AMP-activated Protein Kinase by Metformin Prevents Progression of Heart Failure in Dogs; Involvement of eNOS Activation (2008)
  • Author(s): Sasaki H, Asanuma H, Fujita M, Takahama H, Asakura M, Kim J, Minamino T, Takashima S, Sanada S, Ito S, Min K, Komamura K, Mochizuki N, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会 2008
  • Year and Date: 20080000
• [Presentation] Distinct Regulation of Cardiac Function by Histone Deacetylase Inhibitors in Response to Pressure Overload (2008)
  • Author(s): Me J, Minamino T, Asano Y, Liao YL, Kitakaze M, Wang SW
  • Organizer: 米国心臓協会年次学術集会 2008
  • Year and Date: 20080000
• [Presentation] Usefulness of Exon Array Analysis for Elucidation of Pathogenesis of Heart Failure - Alterations of Splicing Patterns In Murine Failing Hearts (2008)
  • Author(s): Ito S, Asakura M, Liao YL, Min K, Ogai A, Asanuma H, Takahama H, Sasaki H, Kim J, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会 2008
  • Year and Date: 20080000
• [Presentation] Management of Hyperphosphatemia Is an Important Novel Therapeutic Target In Chronic Heart Failure (2008)
  • Author(s): Asanuma H, Asakura M, Kim J, Takahama H, Sasaki H, Sanada S, Ohara T, Min K, Ito S, Fujita M, Asano Y, Takashima S, Minamino T, Komamura K, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会 2008
  • Year and Date: 20080000
• [Presentation] Paradigm Shift to Epigenetic Memory for the Pathological Understanding of Chronic Heart Failure (2008)
  • Author(s): Asano Y, Takashima S, Liao YL, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会 2008
  • Year and Date: 20080000
• [Presentation] Polyethylene-glycol coated liposomal adenosine attenuates hypotension and bradycardia and augments cardioprotection against ischemia/repertusion injury in rats - Nano-size drug delivery system targeted to infarcted myocardium (2007)
  • Author(s): Takahama H, Minamino T, Asanuma H, Fujita M, Wakeno M, Asakura M, Kim J, Takashima S, Komamura K, Hori M, Mochizuki N, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会 2007
  • Year and Date: 20070000
• [Presentation] Usefulness of carperitide as an adjunctive therapy for acute myocardial infarction in patients with chronic kidney disease - Subgroup analysis of J-WIND-ANP trial (2007)
  • Author(s): Asakura M, Kim J, Asanuma H, Myoishi M, Seguchi O, Shintani Y, Tomoike H, Kitakaze M
  • Organizer: 米国心臓協会年次学術集会 2007
  • Year and Date: 20070000
• [Book] 心不全をどうとらえるか (2007)
  • Author(s): 北風政史
  • Publisher: 医学書院
• [Book] 心筋虚血 (2007)
  • Author(s): 浅沼博司、北風政史
  • Publisher: 日本臨床社