Cardioprotection mechanism against stress-induced cardiac injury: analysis based on the regulation of signal transduction by SOCS

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kurume University
• Principal Investigator: YASUKAWA Hideo 久留米大学, 医学部, 准教授 (60289361)
• Project Period (FY): 2011 – 2013
• Keywords: 心筋障害 / サイトカイン / JAK-STAT3 / SOCS3 / ミトコンドリア

Research Abstract

We found that cardiac injury and dysfunction after ischemia-reperfusion or doxorubicin administration were prevented in cardiac-specific gene knockout (KO) mice of SOCS3 (suppressor of cytokine signaling-3). To investigate the mechanism for the prevention of cardiac injury and dysfunction after ischemia-reperfusion or doxorubicin administration in cardiac-specific SOCS3-KO mice, we conducted microarray analysis. Microarray analysis revealed that apoptosis related genes and mitochondria and energy metabolism related genes were important for this prevention in SOCS3-KO mice. These results suggest that socs3, which is a negative regulator of Jak-STAT3 signaling pathway, is important for cardioprotection against stress-induced myocardial injury. SOCS3 may be a promising therapeutic target for acute myocardial infarction and heart failure.

Research Products

• [Journal Article] Omentin prevents myocardial ischemic injury through AMPK- and Akt-dependent mechanisms (2014)
  • Author(s): Kataoka Y, Shibata R, Ohashi K, Kambara T, Enomoto T, Uemura Y, Ogura Y, Yuasa D, Matsuo K, Nagata T, Oba T, Yasukawa H, Numaguchi Y, Sone T, Murohara T, Ouchi N
  • Journal Title: J Am Coll Cardiol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Alterations in Coxsackievirus and Adenovirus Receptor (CAR) Confer Susceptibility to Ventricular Arrhythmia with an Ischemic Event (2013)
  • Author(s): Yasukawa H, Oba T, Fukumoto Y
  • Journal Title: J Am Coll Cardiol Volume: 63 Pages: 560-562
  • Peer Reviewed
• [Journal Article] Involvement of circulating myeloid dendritic cells in the pathogenesis of acute Kawasaki disease in human (2013)
  • Author(s): Suda K, Kishimoto S, Nishino H, Takahashi, T, Okamura H, Teramachi Y, Yokoyama T, Yasukawa H, Imaizumi T, Matsuishi T
  • Journal Title: J Clin Exp Cardiology Volume: 4 Pages: 272
  • DOI: 10.4172/2155-9880.1000272
  • Peer Reviewed
• [Journal Article] (2013)
  • Author(s): Koike K, Ueda S, Yamagishi S, Yasukawa H, Kaida Y, Yokoro M, Fukami K, Yoshimura A, Okuda S
  • Journal Title: Clin Immunol Volume: 150 Pages: 78-87
  • Peer Reviewed
• [Journal Article] Screening for Fabry disease in patients with left ventricular hypertrophy (2013)
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Togawa T, Tsukimura T, Kyogoku S, Ohshima H, Minami T, Sakubaba H, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 167 Pages: 1059-1061
  • Peer Reviewed
• [Journal Article] SOCS3: a novel therapeutic target for cardioprotection (2012)
  • Author(s): Yasukawa H, Nagata T, Oba T, Imaizumi T
  • Journal Title: Jak-Stat Volume: 1 Pages: 234-240
  • Peer Reviewed
• [Journal Article] JAK's SOCS : A Mechanism of Inhibition (2012)
  • Author(s): Yoshimura A, Yasukawa H
  • Journal Title: Immunity Volume: 36 Pages: 157-159
  • Peer Reviewed
• [Journal Article] SOCS, inflammation, and autoimmunity (2012)
  • Author(s): Yoshimura A, Suzuki M, Sakaguchi R, Hanada T, Yasukawa H
  • Journal Title: Front Immunol Volume: 3 Pages: 20
  • DOI: 10.3389/fimmu.2012.00020
  • Peer Reviewed
• [Journal Article] Transient reduction and activation of circulating dendritic cells in patients with acute myocardial infarction (2012)
  • Author(s): Fukui D, Yasukawa H, Sugi Y, Nagata T, Kyogoku S, Futamata N, Oba T, Yokoyama T, Yokoyama S, Ueno T, Kage M, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 160 Pages: 216-219
  • Peer Reviewed
• [Journal Article] Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice (2012)
  • Author(s): Ohmura H, Yasukawa H, Minami T, Sugi Y, Oba T, Nagata T, Kyougoku S, Ohshima H, Aoki H, Imaizumi T
  • Journal Title: Hypertens Res Volume: 35 Pages: 1063-1068
  • Peer Reviewed
• [Journal Article] Cardiac-Specific Deletion of SOCS-3 Prevents Development of Left Ventricular Remodeling After Acute Myocardial Infarction (2012)
  • Author(s): Oba T, Yasukawa H, Hoshijima M, Sasaki KI, Futamata N, Fukui D, Mawatari K, Nagata T, Kyogoku S, Ohshima H, Minami T, Nakamura K, Kang D, Yajima T, Knowlton KU, Imaizumi T
  • Journal Title: J Am Coll Cardiol Volume: 59 Pages: 838-852
  • Peer Reviewed
• [Journal Article] 炎症シグナルと心血管リモデリング『特集炎症・免疫からみた心血管病』 (2011)
  • Author(s): 安川秀雄、京極幸子、永田隆信、今泉勉
  • Journal Title: 循環器内科 Volume: 69(6) Pages: 600-606
• [Journal Article] Role of SOCS proteins in inflammation and autoimmune diseases (2011)
  • Author(s): Fukaya T, Suzuki M, Sakaguchi R, Yasukawa H, Yoshimura A
  • Journal Title: Inflamm Regen Volume: 31 Pages: 382-392
• [Journal Article] Absence of SOCS3 in the cardiomyocyte increases mortality in a gp130 dependent manner accompanied by contractile dysfunction and ventricular arrhythmias (2011)
  • Author(s): Yajima T, Murofushi Y, Zhou H, Park S, Housman J, Zhong ZH, Nakamura M, Machida M, Hwang KK, Gu Y, Dalton ND, Yajima T, Yasukawa H, Peterson KL, Knowlton KU
  • Journal Title: Circulation Volume: 124 Pages: 2690-2671
  • Peer Reviewed
• [Journal Article] Pioglitazone Attenuates Atherosclerotic Plaque Inflammation in Impaired Glucose Tolerant or Diabetic Patients in a Glucose-Lowering Independent Manner - A Prospective, Randomized, Comparator-controlled Study Using Serial FDG-PET/CT– (2011)
  • Author(s): Mizoguchi,M, Tahara N, Tahara A, Nitta Y, KodamaN, Oba T, MD, Mawatari K, Yasukawa H, Kaida H, Ishibashi M, Hayabuchi N, Harada H, MD, Ikeda H, Yamagishi S, Imaizumi T
  • Journal Title: JACC Cardiovasc Imaging Volume: 4 Pages: 1110-1118
  • Peer Reviewed
• [Journal Article] Suppressors of Cytokine Signaling (SOCS) Proteins and JAK/STAT Pathways : Regulation of T-Cell Inflammation by SOCS1 and SOCS3 (2011)
  • Author(s): Tamiya T, Kashiwagi I, Takahashi R, Yasukawa H, Yoshimura A
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 31 Pages: 980-5
  • Peer Reviewed
• [Journal Article] Suppression of SOCS3 in macrophages prevents cancer metastasis by modifying macrophage phase and MCP2/CCL8 induction (2011)
  • Author(s): Hiwatashi K, Tamiya T, Hasegawa E, Fukaya T, Hashimoto M, Kakoi K, Kashiwagi I, Kimura A, Inoue N, Morita R, Yasukawa H, Yoshimura A
  • Journal Title: Cancer Lett. Volume: 308 Pages: 172-80
  • Peer Reviewed
• [Journal Article] Neuronal suppressor of cytokine signaling-3 (Socs3) deficiency enhances hypothalamic leptin dependent phosphatidylinositol 3-kinase (PI3K) signaling (2011)
  • Author(s): Metlakunta A, Sahu M, Yasukawa H, Dhillon S, Belsham D, Yoshimura A, Sahu A
  • Journal Title: Am J Physiol Regul Integr Comp Physiol Volume: 300 Pages: R1185-R1193
  • Peer Reviewed
• [Journal Article] Factors Associated with Plasma Ghrelin Level in Japanese General Population (2011)
  • Author(s): Nanjo Y, Adachi H, Hirai Y, Enomoto M, Fukami A, Otsuka M, Yoshikawa K, Yokoi K, Ogata K, Tsukagawa E, Kasahara A, Murayama K, Yasukawa H, Kojima M, Imaizumi T
  • Journal Title: Clin Endocrinol Volume: 74 Pages: 453-458
  • Peer Reviewed
• [Journal Article] Reduction and activation of circulating dendritic cells in patients with decompensated heart failure (2011)
  • Author(s): Sugi Y, Yasukawa H, Kai H, Fukui D, Futamata N, Mawatari K, Oba T, Nagata N, Kyougoku S, Koga M, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 1472 Pages: 258-64
  • Peer Reviewed
• [Presentation] Screening for Fabry Disease in Patients with Left Ventricular Hypertrophy (2013)
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Kyogoku S, Ohshima H, Minami T, Sugi Y, Imaizumi T
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 埼玉
  • Year and Date: 20131128-30
• [Presentation] Important role of renal nerve-mediated erythropoietin production in the cardioprotection during remote ischemic preconditioning (2013)
  • Author(s): Yasukawa H
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 埼玉
  • Year and Date: 20131128-30
• [Presentation] Cardiac-Specific Deletion of Suppressor of Cytokine Signaling-3 Prevents Doxorubicin-Induced Cardiomyopathy in Mice (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Yajima T, Hoshijima M, Aoki H, Knowlton KU, Imaizumi T
  • Organizer: The American Heart Association, The 85th Scientific Sessions
  • Place of Presentation: Los Angels, USA
  • Year and Date: 20121103-07
• [Presentation] Pioglitazone Decreases Plasma Fibroblast Growth Factor-21 Levels in Patients with Type 2 Diabetes (2012)
  • Author(s): Mawatari K, Tahara N, Yasukawa H, Oba T, Nagata T, Kyougoku S, Ohshima H, Minami T, Mizoguchi M, Sugi Y, Adachi H, Imaizumi T
  • Organizer: The American Heart Association, The 85th Scientific Sessions
  • Place of Presentation: Los Angels, USA
  • Year and Date: 20121103-07
• [Presentation] Prevention of Doxorubicin-Induced Cardiomyopathy in Cardiac-Specific SOCS3 Deficient Mice by Preserving Energy Metabolism (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Fukui D, Sugi Y, Aoki H, Imaizumi T
  • Organizer: 第29回国際心臓研究学会(ISHR)日本部会総会
  • Place of Presentation: 福岡
  • Year and Date: 20121026-27
• [Presentation] Impaired Angiogenesis During Hindlimb Ischemia in Skeletal Muscle-Specific STAT3 Deficient Mice (2012)
  • Author(s): Ohshima H, Yasukawa H, Nagata T, Kyogoku S, Oba T, Mawatari K, Futamata N, Minami T, Sugi Y, Sasaki K, Imaizumi T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-18
• [Presentation] Activation of hypoxia inducible factor-erythropoietin pathway may prevent acute myocardial injury during remote ischemic preconditioning (2012)
  • Author(s): Oba T, Yasukawa H, Nagata T, Kyougoku S, Futamata N, Mawatari K, Minami T, Sugi Y, Fukui D, Aoki H, Imaizumi T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-18
• [Presentation] Prevention of Left Ventricular Remodeling after Acute Myocardial Infarction in Interleukin-17 Deficient Mice (2012)
  • Author(s): Minami T, Yasukawa H, Nagata T, Oba T, Kyogoku S, Ohshima H, Aoki H, Yoshimura A, Imaizumi T
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-18
• [Presentation] Pioglitazone Decreases Plasma Fibroblast Growth Factor-21 Levels in Patients with Type 2 Diabetes (2012)
  • Author(s): 馬渡一寿、田原宣広、安川秀雄、大場豊治、二又誠義、永田隆信、京極幸子、大島英樹、南知子、溝口ミノリ、足達寿、今泉勉
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-18
• [Presentation] 腎神経を介した臓器連関による心筋保護機構–Remote ischemic preconditioningの臓器保護メカニズム− (2012)
  • Author(s): 安川秀雄、大場豊治、青木浩樹、今泉勉
  • Organizer: 第16回日本心血管内分泌代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2012-11-24
• [Presentation] Impaired Angiogenesis During Hindlimb Ischemia in Skeletal Muscle-Specific STAT3 Deficient Mice (2011)
  • Author(s): Ohshima H, Yasukawa H, Nagata T, Kyogoku S, Oba T, Mawatari K, Futamata N, Minami T, Sugi Y, Sasaki K, Imaizumi T
  • Organizer: The American Heart Association, The 84th Scientific Sessions
  • Place of Presentation: Orlando, USA
  • Year and Date: 20111112-17
• [Presentation] Activation of Hypoxia Inducible Factor-Erythropoietin Pathway May Prevent Acute Myocardial Injury During Remote Ischemic Preconditioning (2011)
  • Author(s): Oba T, Yasukawa H, Nagata T, Kyougoku S, Futamata N, Mawatari K, Minami T, Sugi Y, Fukui D, Aoki H, Imaizumi T
  • Organizer: The American Heart Association, The 84th Scientific Sessions
  • Place of Presentation: Orlando, USA
  • Year and Date: 20111112-17
• [Presentation] Prevention of Myocardial Ischemia-Reperfusion Injury in Cardiac-Specific SOCS3 Knockout Mice by Inhibiting Pro-inflammatory Pathways (2011)
  • Author(s): Nagata T, Yasukawa H, Oba T, Pradervans S, Mawatari K, Kyogoku S, Ohshima H, Minami T, Sasaki K, Yajima T, Hoshijima M, Knowlton KU, Imaizumi T
  • Organizer: The American Heart Association, The 84th Scientific Sessions
  • Place of Presentation: Orlando, USA
  • Year and Date: 20111112-17
• [Presentation] Skeletal Muscle-Specific Deletion of STAT3 Impaired Angiogenesis During Hindlimb Ischemia (2011)
  • Author(s): Ohshima H, Yasukawa H, Nagata T, Kyogoku S, Oba T, Mawatari K, Futamata N, Sasaki K, Imaizumi T
  • Organizer: 第75回日本循環器学会
  • Place of Presentation: 横浜
  • Year and Date: 20110803-04
• [Presentation] Cardiac-specific Delation of SOCS-3 Prevents the Doxorubicin-Induced Cardiac Dysfunction in Mice (2011)
  • Author(s): Kyogoku S, Yasukawa H, Oba T, Mawatari K, Nagata T, Ohshima H, Minami T, Imaizumi T
  • Organizer: 第75回日本循環器学会
  • Place of Presentation: 横浜
  • Year and Date: 20110803-04
• [Presentation] Prevention of Myocardial Ischemia-Reperfusion Injury in Cardiac-Specific SOCS3 Knockout Mice by Inhibiting Pro-inflammatory Pathways (2011)
  • Author(s): Nagata T, Yasukawa H, Oba T, Futamata N, Mawatari K, Kyogoku S, Ohshima H, , Imaizumi T
  • Organizer: 第75回日本循環器学会
  • Place of Presentation: 横浜
  • Year and Date: 20110803-04
• [Remarks]
  • URL: http://www.kurume-shinzo.com
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/kucri/