The role of adponectin in regulation of cardiac remodeling

• Project/Area Number: 19689016
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Nagoya University
• Principal Investigator: SHIBATA Rei Nagoya University, 大学院・医学系研究科, 特任講師 (70343689)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000); Fiscal Year 2008: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2007: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
• Keywords: 心血管リモデリング / 脂肪細胞由来因子 / アディポネクチン / 血管内皮前駆細胞 / 心臓 / 血管新生 / 心血管病 / リモデリング

Research Abstract

メタボリックシンドロームに関連した心血管病の病態には、種々の脂肪細胞由来因子の産生異常が関わっている。特にアディポネクチンは、抗糖尿病、抗動脈硬化作用を有し、心血管病の病態にも深く関与している。我々は、アディポネクチンが血管新生作用や心臓肥大抑制作用、抗アポトーシス作用、抗炎症作用、繊維化抑制作用を介して、心血管リモデリング予防効果を発揮することを明らかとした。この結果、アディポネクチンを上昇させる薬剤や治療法の開発、アディポネクチン受容体に対する作動薬の開発が心血管病の新しい治療法につながる可能性を示唆している。

Research Products

• [Journal Article] Adiponectin deficiency exacerbates cardiac dysfunction following pressure overload through disruption of an AMPK-dependent angiogenic response. (2010)
  • Author(s): Shimano M, Ouchi N, Shibata R, Ohashi K, Pimentel DR, Murohara T, Walsh K.
  • Journal Title: J Mol Cell Cardiol. (in press)
  • Peer Reviewed
• [Journal Article] Impact of a single intracoronary administration of adiponectin on myocardial ischemia/reperfusion injury in pig model. (2010)
  • Author(s): Kondo K, Shibata R (責任著者), Unno K, Shimano M, Ishii M, Kito T, Shintani S, Walsh K, Ouchi N, Murohara T.
  • Journal Title: Circ; Cardiovascular Interventions. (in press)
  • Peer Reviewed
• [Journal Article] Adiponectin acts as a positive indicator of left ventricular diastolic dysfunction in patients with hypertrophic cardiomyopathy. (2010)
  • Author(s): Unno K, Shibata R, Izawa H, Hirashiki A, Murase Y, Yamada T, Kobayashi M, Noda A, Nagata K, Ouchi N, Murohara T.
  • Journal Title: Heart. (in press)
  • Peer Reviewed
• [Journal Article] Evidence for the importance of adiponectin in the cardioprotective effects of pioglitazon. (2010)
  • Author(s): Li P, Shibata R, Unno K, Shimano M, Furukawa M, Ohashi T, Cheng X, Nagata K, Ouchi N, Murohara T.
  • Journal Title: Hypertension. 55(1) Pages: 69-75
  • Peer Reviewed
• [Journal Article] Reactive oxidative metabolites are associated with atrial conduction disturbance in patients with atrial fibrillation. (2009)
  • Author(s): Shimano M, Shibata R, Inden Y, Yoshida N, Uchikawa T, Tsuji Y, Murohara T.
  • Journal Title: Heart Rhythm. 6(7) Pages: 935-940
  • Peer Reviewed
• [Journal Article] Caloric restriction stimulates revascularization in response to ischemia via adiponectin-mediated activation of endothelial nitric-oxide synthase. (2009)
  • Author(s): Kondo M, Shibata R, Miura R, Shimano M, Kondo K, Li P, Ohashi T, Kihara S, Maeda N, Walsh K, Ouchi N, Murohara T.
  • Journal Title: J Biol Chem. 284(3) Pages: 1718-1724
  • Peer Reviewed
• [Journal Article] Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis. (2009)
  • Author(s): Kondo K, Shintani S, Shibata R, Murakami H, Murakami R, Imaizumi M, Kitagawa Y, Murohara T.
  • Journal Title: Arterioscler Thromb Vasc Biol. 29(1) Pages: 61-66
  • Peer Reviewed
• [Journal Article] Plasma adiponectin as a predictive factor of survival after a bypass operation for peripheral arterial disease. (2009)
  • Author(s): Komai H, Shibata R, Juri M, Matsushita K, Ouchi N, Murohara T.
  • Journal Title: J Vasc Surg. 50(1) Pages: 95-99
  • Peer Reviewed
• [Journal Article] Adiponectin and cardiovascular disease. (2009)
  • Author(s): Shibata R, Ouchi N, Murohara T.
  • Journal Title: Circ J. 73(4) Pages: 608-614
  • NAID: 10025928845
  • Peer Reviewed
• [Journal Article] Implantation of Adipose-Derived Stem Cells Enhances Ischemia-induced Angiogenesis Role of SDF-1 and Endothelial Progenitor Cells. (2009)
  • Author(s): Kondo K, et al.
  • Journal Title: Arterioscler Thromb Vase Biol 29(1) Pages: 61-66
  • Peer Reviewed
• [Journal Article] Caloric restriction stimulates revascularization in responseto ischemia via adiponectin-mediated activation of eNOS (2009)
  • Author(s): Kondo M, et al.
  • Journal Title: J Biol Chem 284(3) Pages: 1718-1724
  • Peer Reviewed
• [Journal Article] Circulating adiponectin levels in patients with atrial fibrillation. (2008)
  • Author(s): Shimano M, Shibata R, Tsuji Y, Kamiya H, Uchikawa T, Harata S, Muto M, Ouchi N, Inden Y, Murohara T.
  • Journal Title: Circ J. 72(7) Pages: 1120-1124
  • NAID: 110006792065
  • Peer Reviewed
• [Journal Article] Adiponectin promotes endothelial progenitor cell number and function. (2008)
  • Author(s): Shibata R, Skurk C, Ouchi N, Galasso G, Kondo K, Ohashi T, Shimano M, Kihara S, Murohara T, Walsh K.
  • Journal Title: FEBS Lett. 582(11) Pages: 1607-1612
  • Peer Reviewed
• [Journal Article] Usefulness of adiponectin to predict myocardial salvage following successful reperfusion in patients with acute myocardial infarction. (2008)
  • Author(s): Shibata R, Numaguchi Y, Matsushita K, Sone T, Kubota R, Ohashi T, Ishii M, Kihara S, Walsh K, Ouchi N, Murohara T.
  • Journal Title: Am J Cardiol. 101(12) Pages: 1712-1715
  • Peer Reviewed
• [Journal Article] Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase dependent mechanisms. (2008)
  • Author(s): Nishimura M, Izumiya Y, Higuchi A, Shibata R, Qiu J, Kudo C, Shin HK, Moskowitz MA, Ouchi N.
  • Journal Title: Circulation. 117(2) Pages: 216-223
  • Peer Reviewed
• [Journal Article] Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive hypertension: role of activation of AMP-activated protein kinase and inhibition of Akt. (2008)
  • Author(s): Kato MF, Shibata R, Obata K, Miyachi M, Yazawa H, Tsuboi K, Yamada T, Nishizawa T, Noda A, Cheng XW, Murate T, Koike Y, Murohara T, Yokota M, Nagata K.
  • Journal Title: J Hypertens. 26(8) Pages: 1669-1676
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes. (2008)
  • Author(s): Ikeda Y, Ohashi K, Shibata R, Pimentel DR, Kihara S, Ouchi N, Walsh K.
  • Journal Title: FEBS Lett. 582(7) Pages: 1147-1150
  • Peer Reviewed
• [Journal Article] Adiponectin prevents cerebral ischemic injury through eNOS-dependent mechanisms. (2008)
  • Author(s): Nishimura M, et al.
  • Journal Title: Circulation 117(2) Pages: 216-223
  • Peer Reviewed
• [Journal Article] Angiopoietin-related growth factor enhances blood flow via activation of the ERK1/2-eNOS pathway in a mouse hind-limb ischemia model. (2008)
  • Author(s): Urano T, et al.
  • Journal Title: Arterioscler Thromb Vase Biol 28(5) Pages: 827-834
  • Peer Reviewed
• [Journal Article] Usefulness of Adiponectin to Predict Myocardial Salvage Following Successful Reperfusion in Patients with Acute Myocardial Infarction. (2008)
  • Author(s): Shibata R, et al.
  • Journal Title: Am J Cardiol 101(12) Pages: 1712-1715
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes. (2008)
  • Author(s): Ikeda Y, et al.
  • Journal Title: FEBS Lett 582(7) Pages: 1147-1150
  • Peer Reviewed
• [Journal Article] Adiponectin promotes endothelial progenitor cell number and function. (2008)
  • Author(s): Shibata R, et al.
  • Journal Title: FEBS Lett 582(11) Pages: 1607-1610
  • Peer Reviewed
• [Journal Article] Circulating adiponectin levels in patients with atrial fibrillation (2008)
  • Author(s): Shimano M, et al.
  • Journal Title: Circ J 72(7) Pages: 1120-1124
  • Peer Reviewed
• [Journal Article] Circulating homocysteine levels in patients with radiofrequency catheter ablation for atrial fibrillation. (2008)
  • Author(s): Shimano M, et al.
  • Journal Title: Europace. 10(8) Pages: 961-966
  • Peer Reviewed
• [Journal Article] Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive hypertension : role of activation of AMP-activated protein kinase and inhibition of Akt. (2008)
  • Author(s): Kato MF, et al.
  • Journal Title: J Hypertens 26(8) Pages: 1669-1676
  • Peer Reviewed
• [Journal Article] Homocysteine and heavy metal interactions in atrial fibrillation and ablation treatments (2008)
  • Author(s): Shimano M, et al.
  • Journal Title: Europace 10(12) Pages: 1458-1459
  • Peer Reviewed
• [Journal Article] Adiponectin prevents cerebral ischemic injury through eNOS-dependent mechanisms. (2008)
  • Author(s): Nishimura M, et. al.
  • Journal Title: Circulation 117(2) Pages: 216-23
  • Peer Reviewed
• [Journal Article] Angiopoietin-related growth factor enhances blood flow via activation of the ESK1/2-eNOS pathway in a mouse hind-limb ischemia model. (2008)
  • Author(s): Urano T, et. al.
  • Journal Title: Arterioscler Thromb Vase Biol (印刷中)
  • Peer Reviewed
• [Journal Article] Usefulness of Adiponectin to Predict Myocardial Salvage Following Successful Reperfusion in Patients with Acute Myocardial Infarction. (2008)
  • Author(s): Shibata R, et. al.
  • Journal Title: Am J Cardiol (印刷中)
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 induction by adiponectin is regulated bya sphingosine kinase-1 dependent mechanism in cardiac myocytes. (2008)
  • Author(s): Ikeda Y, et. al.
  • Journal Title: FEBS Lett (印刷中)
  • Peer Reviewed
• [Journal Article] Circulating adiponectin levels in patients with atrial fibrillation (2008)
  • Author(s): Shimano M, et. al.
  • Journal Title: Circ J (印刷中)
  • Peer Reviewed
• [Journal Article] Potential of adiponectin as a cardioprotective agent. (2007)
  • Author(s): Shibata R, Ouchi N, Walsh K, Murohara T.
  • Journal Title: Future Cardiol. 3(6) Pages: 647-656
  • Peer Reviewed
• [Journal Article] Adiponectin protects against the development of systolic dysfunction following myocardial infarction. (2007)
  • Author(s): Shibata R, Izumiya Y, Sato K, Papanicolaou K, Kihara S, Colucci WS, Sam F, Ouchi N, Walsh K.
  • Journal Title: J Mol Cell Cardiol. 42(6) Pages: 1065-1074
  • Peer Reviewed
• [Journal Article] Adiponectin accumulates in myocardial tissue that has been damaged by ischemia-reperfusion injury via leakage from the vascular compartment. (2007)
  • Author(s): Shibata R, et. al.
  • Journal Title: Cardiovasc Res 74(3) Pages: 471-9
  • Peer Reviewed
• [Journal Article] Adiponectin protects against the development of systolic dysfunction following myocardial infarction. (2007)
  • Author(s): Shibata R, et. al.
  • Journal Title: J Mol Cell Cardiol 42(6) Pages: 1065-74
  • Peer Reviewed
• [Journal Article] The potential of adiponectin as a cardioprotective agent. (2007)
  • Author(s): Shibata R, et. al.
  • Journal Title: Future Cardiology 6 Pages: 647-656
  • Peer Reviewed
• [Journal Article] Adiponectin actions in the cardiovascular system. (2007)
  • Author(s): Hopkins TA, et. al.
  • Journal Title: Cardiovasc Res 74(1) Pages: 11-8
  • Peer Reviewed
• [Presentation] Role of adiponectin in regulation of cardiac remodeling (2010)
  • Author(s): 柴田玲
  • Organizer: 第74回日本循環器病学会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-05
• [Presentation] Fenofibrate mediates angiogenesis in response to ischemia via adiponectin-mediated LKB1 /AMPK dependent mechanism (2010)
  • Author(s): Li P, Shibata R, Murohara T
  • Organizer: 第74回日本循環器病学会:国際留学生Young Investigator Award優秀賞
  • Place of Presentation: 京都
  • Year and Date: 2010-03-05
• [Presentation] アディポサイトカインと循環器疾患 (2009)
  • Author(s): 柴田玲
  • Organizer: 第13回日本心不全学会
  • Place of Presentation: 福岡国際会議場モーニングレクチャー
  • Year and Date: 2009-10-31
• [Presentation] Impact of a single intracoronary administration of adiponectin on myocardial ischemia / reperfusion injury in pig model (2009)
  • Author(s): 柴田玲、近藤和久、室原豊明
  • Organizer: 第13回日本心不全学会優秀賞
  • Place of Presentation: 福岡
  • Year and Date: 2009-10-30
• [Presentation] Caloric restriction stimulates ischemia-induced angiogenesis via adiponectin-mediated activation of eNOS. (2009)
  • Author(s): Shibata R, Walsh K, Ouchi N, Murohara T.
  • Organizer: The XV International Symposium on Atherosclerosis
  • Place of Presentation: USA New Orleans
  • Year and Date: 2009-06-15
• [Presentation] 脂肪細胞由来因子アディポネクチンのNOを介した血管新生作用 (2009)
  • Author(s): 柴田玲
  • Organizer: 第9回日本NO学会
  • Place of Presentation: 静岡
  • Year and Date: 2009-05-09
• [Presentation] アディポサイトカインと循環器疾患 (2009)
  • Author(s): 柴田玲
  • Organizer: 第73回日本循環器病学会
  • Place of Presentation: 大阪国際会議場ランチョンセミナー
  • Year and Date: 2009-03-22
• [Presentation] Pioglitazone Attenuates Angiotensin II-induced Cardiac Hypertrophy and Fibrosis Through Stimulation of Adiponectin Secretion (2009)
  • Author(s): Li P, Shibata R, Murohara T
  • Organizer: 第73回日本循環器病学会:国際留学生Young Investigator Award優秀賞
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [Presentation] Caloric Restriction Stimulates Ischemia-induced Angiogenesis through an eNOS-dependent Pathway. (2008)
  • Author(s): Shibata R, et al.
  • Organizer: The Scientific Sessions of American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-15
• [Presentation] Pioglitazone Attenuates Angiotensin Ii-Induced Cardiac Hypertrophy and Fibrosis Through Stimulation of Adiponectin Secretion. (2008)
  • Author(s): Ping Li, et al.
  • Organizer: The Scientific Sessions of American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-15
• [Presentation] Plasma Adiponectin Levels in Patients with Atrial Fibrillation. (2008)
  • Author(s): Shimano M, et al.
  • Organizer: The Scientific Sessions of American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-15
• [Presentation] Adiponectin predicts myocardial salvage following successful reperfusion in patients with acute myocardial infarction (2008)
  • Author(s): 柴田玲、沼口靖、大内乗有、Kenneth Walsh、室原豊明
  • Organizer: 第56回日本心臓病学会Young Investigator Award最優秀賞
  • Place of Presentation: 東京
  • Year and Date: 2008-09-08
• [Presentation] Adiponectin predicts myocardial salvage following successful reperfusion in patients with acute myocardial infarction (2008)
  • Author(s): Shibata R, et al.
  • Organizer: 第56回日本心臓病学会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-08
• [Presentation] Adiponectin predicts myocardial salvage following successful reperfusion in patients with acute myocardial infarction (2008)
  • Author(s): Shibata R, et. al.
  • Organizer: 第72回日本循環器学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Calorie restriction mediates angiogenesis in response to tissue ischemia thorough stimulation of adiponectin secretion (2008)
  • Author(s): Kondo M, et. al.
  • Organizer: 第72回日本循環器学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Calorie restriction induces angiogenesis in response to tissue ischemia thorough modulation of endothelial progenitor cell mobilization (2008)
  • Author(s): Miura R, et. al.
  • Organizer: 第72回日本循環器学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Circulating adiponectin levels in patients with atrial fibrillation (2008)
  • Author(s): Shimano M, et. al.
  • Organizer: 第72回日本循環器学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] 急性心筋梗塞におけるアディポネクチンの意義〜血管内皮前駆細胞との関連 (2007)
  • Author(s): Shibata R, et. al.
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-11-29
• [Presentation] 急性心筋梗塞におけるアディポネクチンの意義〜血管内皮前駆細胞との連関 (2007)
  • Author(s): Shibata R, et. al.
  • Organizer: 第11回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-16
• [Book] 痩せりゃいい、ってもんじゃない!-脂肪の科学 (2008)
  • Author(s): 森永卓郎, 柴田玲
  • Total Pages: 166
  • Publisher: 文春新書
• [Book] 痩せりゃいい、ってもんじゃない!-脂肪の科学 (2008)
  • Author(s): 森永卓郎、柴田玲
  • Total Pages: 166
  • Publisher: 文春新書
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/junnai/junnai/
• [Remarks] 2009年第56回日本心臓病学会Young Investigator Award最優秀賞
• [Remarks] 2009年第13回日本心不全学会Young Investigator Award優秀賞
• [Patent(Industrial Property Rights)] THERAPEUTIC APPLICATION OF ADIPONECTIN IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION (2010)
  • Inventor(s): 柴田玲、室原豊明
  • Industrial Property Rights Holder: 名古屋大学
  • Filing Date: 2010-02-26