Comprehensive analysis of pathogenesis and etiology of Takotsubo Cardiomyopathy by use of experimental model animal

• Project/Area Number: 21590771
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Wakayama Medical University
• Principal Investigator: UEYAMA Takashi 和歌山県立医科大学, 医学部, 准教授 (50264875)
• Co-Investigator(Kenkyū-buntansha): KAWABE Tetsuya 和歌山県立医科大学, 医学部, 助教 (60508034) ; KIMURA Hiroko 順天堂大学, 医学部, 准教授 (00053299) ; TSURUO Yoshihiro 和歌山県立医科大学, 医学部, 教授 (90207449)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ストレス / 心身症 / モデル動物 / 脳 / 心臓 / 網羅的発現解析 / 酸化的ストレス / 綱羅的発現解析

Research Abstract

We investigated the pathogenesis and etiology of Takotsubo Cardiomyopathy by use of stress-induced rat model. Activation of α1-adrenoceptor in the blood vessels or activation ofβ1-adrenoceptors in the heart was mainly responsible for emotional stress-induced alteration of cardiac and vascular genes profiles. All amygdalid subncleui receive psychological information from other limbic brain, while the lateral and central subnuclei receive peripheral and sensory information. Output to the hypothalamus and peripheral sympathetic system mainly originates from the medial amygdala.

Research Products

• [Journal Article] Cardiac and vascular gene profiles in an animal model of takotsubo cardiomyopathy (2011)
  • Author(s): Ueyama T, Yamamoto, Y, Ueda K, Kawabe T, Hano T, Ito T, Tsuruo Y, Ichinose M, Yoshida K
  • Journal Title: Heart and Vessels Volume: 26 Pages: 321-337
  • NAID: 10029835153
  • Peer Reviewed
• [Journal Article] 中枢自律神経系 (2011)
  • Author(s): 上山敬司、仙波恵美子
  • Journal Title: 分子精神医学 Volume: 11 Pages: 8-13
• [Journal Article] 視床下部視交叉上核の神経回路 (2011)
  • Author(s): 上山敬司
  • Journal Title: 自律神経 Volume: 48 Pages: 120-121
  • NAID: 10029303935
  • Peer Reviewed
• [Journal Article] Cardiac and vascular gene profiles in an animal model of takotsubo cardiomyopathy. (2011)
  • Author(s): Ueyama T, et al
  • Journal Title: Heart and Vessels Volume: 26 Pages: 321-337
  • NAID: 10029835153
  • Peer Reviewed
• [Journal Article] たこつぼ心筋症の基礎.病態心臓 (2010)
  • Author(s): 上山敬司
  • Volume: 42
  • Pages: 426-430
• [Journal Article] Stress cardiomyopathy (2010)
  • Author(s): Akashi YJ, Nef HM, Mollmann H, Ueyama T
  • Journal Title: Annu Rev Med Volume: 61 Pages: 271-86
  • Peer Reviewed
• [Journal Article] 圧受容体反射に及ぼすストレス関連ペプチドの影響 (2010)
  • Author(s): 川辺哲也、上山敬司、鶴尾吉宏、羽野卓三
  • Journal Title: 自律神経 Volume: 47 Pages: 221-225
  • NAID: 10026905638
  • Peer Reviewed
• [Journal Article] 精神性ストレス時の循環反応に対するエストロゲンの抑制作用と酸化ストレスの関与 (2010)
  • Author(s): 森本恵子、上山敬司
  • Journal Title: 自律神経 Volume: 47 Pages: 321-327
  • NAID: 10026905970
  • Peer Reviewed
• [Journal Article] 視床下部視交叉上核から自律神経系への神経回路 (2010)
  • Author(s): 上山敬司
  • Journal Title: 循環器内科 Volume: 68 Pages: 434-440
• [Journal Article] Connexin-43 Redistribution and Gap Junction Activation During Forced Restraint Protects Against Sudden Arrhythmic Death in Rats (2010)
  • Author(s): Unuma K, Shintani-Ishida K, Tsushima K, Shimosawa T, Ueyama T, Kuwahara M, Yoshida K
  • Journal Title: Circ J Volume: 74 Pages: 1087-1095
  • NAID: 10026474454
  • Peer Reviewed
• [Journal Article] Restraint Stress Induces Connexin-43 Translocation via α-Adrenoceptors in Rat Heart (2010)
  • Author(s): Unuma K, Kaori Shintani-Ishida K, Yahagi N, Tsushima K, Shimosawa T, Ueyama T, Yoshida K
  • Journal Title: Circ J Volume: 74 Pages: 2693-2701
  • NAID: 10027424654
  • URL: http://dx.doi.org/10.1253/circj.CJ-10-0529
  • Peer Reviewed
• [Journal Article] 情動的ストレスによる、心血管系での酸化的ストレス応答 (2010)
  • Author(s): 上山敬司
  • Journal Title: 心身医学 Volume: 5 Pages: 879-884
• [Journal Article] Stress Cardiomyopathy. (2010)
  • Author(s): Akashi, YJ, et al
  • Journal Title: Ann Rev Med Volume: 61 Pages: 271-286
  • Peer Reviewed
• [Journal Article] Connexin-43 Redistribution and Gap Junction Activation During Forced Restraint Protects Against Sudden Arrhythmic Death in Rats. (2010)
  • Author(s): Unuma K, et al
  • Journal Title: Circ J Volume: 74 Pages: 1087-1095
  • Peer Reviewed
• [Journal Article] Restraint Stress Induces Connexin-43 Translocation via α-Adrenoceptors in Rat Heart. (2010)
  • Author(s): Unuma K, et al
  • Journal Title: Circ J Volume: 74 Pages: 2693-2701
  • Peer Reviewed
• [Journal Article] たこつぼ心筋症の基礎・病態 (2010)
  • Author(s): 上山敬司
  • Journal Title: 心臓 Volume: 42 Pages: 426-430
  • NAID: 130002147155
• [Journal Article] 受容体反射に及ぼすストレス関連ペプチドの影響 (2010)
  • Author(s): 川辺哲也, 他
  • Journal Title: 自律神経 Volume: 47 Pages: 221-225
• [Journal Article] 視床下部視交叉田上核から自律神経系への神経回路 (2010)
  • Author(s): 上山敬司
  • Journal Title: 循環器科 Volume: 68 Pages: 434-440
• [Journal Article] たこつぼ心筋症とその動物モデル (2009)
  • Author(s): 上山敬司, 石蔵文信
  • Journal Title: 心身医学 Volume: 49 Pages: 869-874
• [Journal Article] 自律神経の中枢神経回路の解析 (2009)
  • Author(s): 上山敬司
  • Journal Title: 自律神経 Volume: 46 Pages: 147-155
  • NAID: 10025570965
• [Journal Article] たこつぼ心筋症モデルにおける、ヘムオキシゲナーゼの増加 (2009)
  • Author(s): 上山敬司, 鶴尾吉宏
  • Journal Title: 自律神経 Volume: 46 Pages: 558-560
  • NAID: 10026904800
  • Peer Reviewed
• [Journal Article] たこつぼ型心筋症の機序-動物実験からの新規視点 (2009)
  • Author(s): 上山敬司
  • Journal Title: 循環器科 Volume: 66 Pages: 229-236
• [Journal Article] Up-regulation of hemeoxygenase 1 in an animal model of takotsubo cardiomyopathy (2009)
  • Author(s): Ueyama T, Kawabe T, Hano T, Tsuruo Y, Ueda K, Ichinose M, Kimura H, Yoshida K
  • Journal Title: Circ J Volume: 73 Pages: 1141-1146
  • NAID: 10026904800
  • URL: http://dx.doi.org/10.1253/circj.CJ-08-0988
  • Peer Reviewed
• [Journal Article] Polaprezinc(zinc L-carnosine) is a potent inducer of anti-oxidative stress enzyme, heme oxygenase(HO) 1-a new mechanism of gastric mucosal protection. (2009)
  • Author(s): Ueda K, Ueyama T, Oka M, Ito T, Tsuruo Y, Ichinose M
  • Journal Title: J Pharma Sci Volume: 110 Pages: 285-294
  • NAID: 10025737558
  • Peer Reviewed
• [Journal Article] Stress Cardiomyopathy (2009)
  • Author(s): Akashi, YJ, et al
  • Journal Title: Ann Rev Med, E-pub 61
  • Peer Reviewed
• [Journal Article] Up-regulation of hemeoxygenase 1 in an animal model of takotsubo cardiomyopathy (2009)
  • Author(s): 上山敬司, et al
  • Journal Title: Circ J 73 Pages: 1141-1146
  • NAID: 10026904800
  • Peer Reviewed
• [Journal Article] Polaprezinc(zinc L-carnosine)is a potent inducer of anti-oxidative stress enzyme, heme oxygenase(HO)1-a new mechanism of gastric mucosal protection (2009)
  • Author(s): Ueda K, et al
  • Journal Title: J Pharma Sci 110 Pages: 285-294
  • Peer Reviewed
• [Journal Article] たこつぼ心筋症モデルにおける、ヘムオキシゲナーゼの増加 (2009)
  • Author(s): 上山敬司, 他
  • Journal Title: 自律神経 46 Pages: 558-560
  • NAID: 10026904800
  • Peer Reviewed
• [Journal Article] たこつぼ心筋症とその動物モデル (2009)
  • Author(s): 上山敬司, 他
  • Journal Title: 心身医学 49 Pages: 869-874
  • Peer Reviewed
• [Journal Article] 自律神経の中枢神経回路の解析 (2009)
  • Author(s): 上山敬司
  • Journal Title: 自律神経 46 Pages: 147-155
  • NAID: 10025570965
• [Journal Article] たこつぼ型心筋症の機序-動物実験からの新規視点 (2009)
  • Author(s): 上山敬司
  • Journal Title: 循環器科 66 Pages: 229-236
• [Journal Article] 辺縁系と自律神経系
  • Author(s): 上山敬司、仙波恵美子
  • Journal Title: 臨床神経
  • URL: http://dx.doi.org/10.5692/clinicalneurol.50.1003
• [Presentation] Afferent projection to amygdaloid subnuclei and intrinsic connection of each subnuclei (2012)
  • Author(s): 上山敬司, 他
  • Organizer: 第117回日本解剖学会総会・全国学術集会合同大会
  • Place of Presentation: 甲府
• [Presentation] たこつぼ心筋症動物モデルにおいて、心血管系に発現する遺伝子群の網羅的解析 (2011)
  • Author(s): 上山敬司
  • Organizer: 第52回日本心身医学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-06-09
• [Presentation] Cardiac and vascular molecular responses in emotional stress-induced acute heart failure (2011)
  • Author(s): Ueyama T
  • Organizer: The Tenth Symposium on Catecholamines and other Neurotransmitters in Stress
  • Place of Presentation: Smolenice Castle, Slovakia
• [Presentation] Signal transduction from limbic brain to the heart in the emotinal stress-induced acute heart failure (2011)
  • Author(s): 上山敬司、山本悠太、伊藤隆雄、鶴尾吉宏
  • Organizer: 第88回日本生理学会大会第116回日本解剖学会総会・全国学術集会合同大会
  • Place of Presentation: 横浜
• [Presentation] Cardiac and vascular molecular responses in emotional stress-induced acute heart failure (2011)
  • Author(s): Ueyama T
  • Organizer: The Tenth Symposium on Catecholamines and other Neurotransmitters in Stress
  • Place of Presentation: Smolenice Castle, Slovakia(招待講演)
• [Presentation] Signal transduction from limbic brain to the heart in the emotional stress-induced acute heart failure (2011)
  • Author(s): 上山敬司, 他
  • Organizer: 第88回日本生理学会大会第116回日本解剖学会総会・全国学術集会合同大会
  • Place of Presentation: 横浜(誌上発表)
• [Presentation] Selective ablation of histamine H1 receptor-expressing neurons in the hypothalamus to study their role in the regulation of food intake (2011)
  • Author(s): 堀尾修平, 他
  • Organizer: 第88回日本生理学会大会第116回日本解剖学会総会・全国学術集会合同大会
  • Place of Presentation: 横浜(誌上発表)
• [Presentation] マウス視床下部室傍核のヒスタミンH1受容体発現ニューロンの死滅による摂食亢進 (2011)
  • Author(s): 堀尾修平, 他
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 兵庫県淡路市
• [Presentation] Signal transduction from limbic brain to the heart in the emotinal stress-induced acute heart failure (2011)
  • Author(s): 上山敬司, 他
  • Organizer: 第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会合同大会
  • Place of Presentation: 横浜
• [Presentation] Selective ablation of histamine H1 receptor-expressing neurons in thehypothalamus to study their role in the regulation of food intake (2011)
  • Author(s): 堀尾修平, 他
  • Organizer: 第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会合同大会
  • Place of Presentation: 横浜
• [Presentation] たこつぼ心筋症動物モデルにおいて、心血管系に発現する遺伝子群の網羅的解析 (2010)
  • Author(s): 上山敬司、山本悠太、川邊哲也、羽野卓三、伊藤隆雄、鶴尾吉宏、吉田謙一
  • Organizer: 第63回日本自律神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-22
• [Presentation] Attenuation of cardiovascular responses to endomorphin-2 microinjections into the nucleus tractus solitarius of the spontaneously hypertensive rat. (2010)
  • Author(s): Kawabe T, et al
  • Organizer: 23rd Scientific Meeting of the International Society of Hypertension.
  • Place of Presentation: Vancouver, Canada.
  • Year and Date: 2010-09-26
• [Presentation] 情動的ストレスによる、心血管系の細胞での酸化的ストレス応答 (2010)
  • Author(s): 上山敬司
  • Organizer: 第51回日本心身医学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2010-06-27
• [Presentation] 辺縁系(特に扁桃体)と自律神経 (2010)
  • Author(s): 上山敬司、仙波恵美子
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] 情動的ストレスによる、cyclooxygenase-2の増加 (2010)
  • Author(s): 上山敬司、伊藤隆雄、鶴尾吉宏
  • Organizer: 第115回日本解剖学会総会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-03-27
• [Presentation] Cardiac gene profiles in an animal model of Takotsubo cardiomyopathy (2010)
  • Author(s): 上山敬司, 川辺哲也, 羽野卓三, 吉田謙一
  • Organizer: 74回日本循環器学会総会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-21
• [Presentation] Cardiac gene profiles in an animal model of Takotsubo cardiomyopathy (2010)
  • Author(s): 上山敬司, 他
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-21
• [Presentation] Hano T Attenuation of cardiovascular responses to endomorphin-2 microinjections into the nucleus tractus solitarius of the spontaneously hypertensive rat (2010)
  • Author(s): Kawabe T, Ueyama T, Tsuruo Y
  • Organizer: 23rd Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Vancouver
• [Presentation] 視床下部視交叉上核から自律神経系への神経回路 (2010)
  • Author(s): 上山敬司
  • Organizer: 第63回日本自律神経学会総会
  • Place of Presentation: 横浜
• [Presentation] たこつぼ心筋症モデルにおける、サイクロオキシゲナーゼの増加 (2009)
  • Author(s): 上山敬司、鶴尾吉宏、川辺哲也、羽野卓三
  • Organizer: 第62回日本自律神経学会総会
  • Place of Presentation: 和歌山
  • Year and Date: 2009-11-05
• [Presentation] 情動的ストレスにより、心血管系の細胞で酸化的ストレスが起こる (2009)
  • Author(s): 上山敬司、伊藤隆雄、鶴尾吉宏
  • Organizer: 第50回日本組織細胞化学会総会
  • Place of Presentation: 大津
  • Year and Date: 2009-09-26
• [Presentation] Effects of estrogen on stress-induced activation of nitric oxide producing neurons in paraventricular hypothalamic neurons of rats (2009)
  • Author(s): Omura Y, et al
  • Organizer: The 36th Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-07-27
• [Presentation] Up-regulation of cyclooxygenase 2 in an Animal Model of Takotsubo Cardiomyopathy (2009)
  • Author(s): 上山敬司, 川辺哲也, 羽野卓三, 吉田謙一
  • Organizer: 第73回日本循環器学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [Presentation] Preventive effects of estrogen and beta blocker on stress-induced cardiac dysfunction in an experimental rat model (2009)
  • Author(s): 石蔵文信、上山敬司
  • Organizer: 第73回日本循環器学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Ichinose M Polaprezinc as a potent inducer of anti-oxidative stress enzyme (2009)
  • Author(s): Ueda K, Ueyama T, Tamai H, Arii K, Yanaoka K, Ito T, Tsuruo Y, Oka M
  • Organizer: Digestive Disease Week
  • Place of Presentation: Chicago, USA
• [Presentation] Morimoto K Effects of estrogen on stress-induced activation of nitric oxide producing neurons in paraventricular hypothalamic neurons of rats (2009)
  • Author(s): Omura Y, Hata T, Hara Y, Takamata A, Ueyama T
  • Organizer: The 36th Congress of the International Union of Physiological Sciences
  • Place of Presentation: Kyoto, Japan