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EXPERIMENTAL STUDY ON THE PATHOGENESIS OF APICAL HYPERTROPHY

Research Project

Project/Area Number 02454263
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionKURUME UNIVERSITY

Principal Investigator

KOGA Yoshinori  KURUME UNIVERSITY; THE 3RD DEPARTMENT OF MEDICINE; ASSOCIATE PROFESSOR, 医学部, 助教授 (50080669)

Co-Investigator(Kenkyū-buntansha) IWAMI Gensho  KURUME UNIVERSITY; THE 3RD DEPARTMENT OF MEDICINE; MEDICAL ASSISTANT, 医学部, 助手 (90203405)
NAKATA Masashi  KURUME UNIVERSITY; THE 3RD DEPARTMENT OF MEDICINE; MEDICAL ASSISTANT, 医学部, 助手 (70180304)
KAJIYAMA Kiminori  KURUME UNIVERSITY; THE 3RD DEPARTMENT OF MEDICINE; ASSISTANT PROFESSOR, 医学部, 講師 (00175275)
中田 真詩  久留米大学, 医学部, 助手 (00227779)
野原 正敏  久留米大学, 医学部, 講師 (90148792)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsApical Hypertrophy / Pressure Overload / Cardiac Hypertrophy / Norepinephrine / Protein Kinase C / Skeletal alpha-actin m-RNA / プロティンキナーゼC / SHR / 圧負荷肥大心 / プロテインキナ-ゼC / 骨格筋型アクチン mーRNA / プロテインキナ-ゼ C / ノルアドレナリン
Research Abstract

Apical hypertrophy, initially reported from Japan, presents several clinical profiles distinct from classical hypertrophic cardiomyopathy, whereas mechanisms for localization of abnormal hypertrophy to the ventricular apex remains to be investigated. The present study hypothesizes that the apical myocardium manifests a greater hypertrophic response to pressure overload associated with higher activation of protein-kinase C (PKC). In Wistar rats and SHR, myocardial norepinephrine content was lower in the apex, and higher in the left ventricular free wall, consistent with reported distribution of the sympathetic nerve. Pressure overload produced by abdominal aortic constriction (AC) induced increases in myocardial norepinephrine levels in both strains, while its local gradient remained unchanged. Myocardial levels of inositol-triphosphate did not show a local gradient. The PKC activity in the apical myocardium was lower in Wistar, but not different in SHR. AC induced significant increases … More in PKC activity in the apical and septal myocardium of SHR, although these increases were not observed in Wistar. These observations suggested that pressure overload could induce differential activation of PKC in some pathological conditions like SHR.
Pressure overload induces isoformic changes in contractile proteins, including myosin heavy chain and alpha-actin. With the primer extension method, we confirmed re-expression of skeletal alpha-actin (s-ACT) m-RNA after AC in Wistar rats. The re-expression of s-ACT m-RNA at 6 hours after AC was greater in the endocardium than in the epicardium, and also higher in the apical endocardium than in the basal endocardium.
These greater activation of PKC and re-expression of s-ACT m-RNA in the apical myocardium at the early developmental stage of pressure overload hypertrophy might be attributed to decreased sympathetic innervation or higher wall stress imposed by elevated pressure. The apical myocardium could thus manifest an enhanced hypertrophic response to pressure overload, that could be related to the pathogenesis of apical hypertrophy. Less

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] 梶山 公則,古賀 義則: "心肥大とカテコールアミン受容体:α受容体とβ受容体の細胞内情報伝達機構" 医学のあゆみ. 154. 757 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 辻 ゆかり,梶山 公則,古賀 義則 他: "自然発症高血圧ブットにおける心筋内カチコールアミンと細胞内情報伝達系の検討" 心臓. 23(Suppl2). 11-14 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 古賀 義則,大月 務,岡 直樹: "心肥大形成のメカニズム2 液性因子による心肥大" 治療学. 26. 1445-1449 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakata M,Chiba M,Koga Y et al: "Predominant expression of skeletal α-actin m-RNA in the left ventricular endocardium and apex at the early stage of prediure overload" Circulation. 84. SUPPL2-49 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Koga Y,Iwami G,Nakata M et al: "Adrenergic and angiotensin systems in cardiac hypertrophy" J Mol Cell Cardiol. 24. SUPPL1-41 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Iwami G,Tsugi T,Koga Y et al: "Activation of PKC and 1P_3 during presure overload by antic constriction in sopntaneously hypertemsive rats" J Mol Cell Cardiol. 24. SUPPL1-61 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 古賀 義則,戸嶋 裕徳: "心・血管系におけるα受容体心肥大におけるアドレナリン受容体の役割" Excerpta Medica東京, 11-26 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 古賀 義則,梶山 公則: "心不全 心肥大:心不全" 南江堂,東京, 262-268 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kajiyama K, Koga Y.: "Cardiac hypertrophy and adrenergic receptors." Igakunoayumi. 154(12). 757 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsuji Y, Kajiyama K, Iwami G, Sufu H, Ohtsuki T, Koga Y, Toshima H.: "Myocardial catecholamines and intracellular signal transduction in spontaneously hypertensive rats." Shinzo. 23(suppl2). 11-14 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Koga Y, Ohtsuki T, Oka N.: "Mechanism for cardiac hypertrophy. -neurohormonal factors-" Chiryogaku. 26(12). 1445-1449 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakata M, Chiba M, Sumida E, Sumida E, Oka N, Koga Y.: "Predominant expression of skeletal alpha-actin mRNA in the left ventricular endocardium and apex at the early stage of pressure overload." Circulation. 84(Supp12.). 49 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Koga Y, Iwami G, Tsuji Y, Oka N, Nakata M, Kajiyama K, Toshima H.: "Adrenergic and angiotensin systems in cardiac hypertrophy." J Mol Cell Cardiol. 24(Suppl 1). 41 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Iwami G, Tsuji Y, Kajiyama K, Ohtsuki T, Sufu H, Koga Y, Toshima H.: "Activation of PKC and IP_3 during pressure overload by aortic constriction in spontaneously hypertensive rats (SHR)." J Mol Cell Cardiol. 24(Suppl 1). 61 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Sumida E, Nohara M, Kaku H, Oka N, Sumida E, Koga Y, Toshima H.: "Altered calcium handling in single pressure overload hypertrophied rat myocytes." J Mol Cell Cardiol. 24(Suppl 1). 212 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kajiyama K, Iwami G, Koga Y, Tsuji Y, Ohtsuki T, Toshima H.: "Pressure overload increases norepinephrine and activates protein kinase C in the myocardium of spontaneously hypertensive rats (SHR)." Cardiovas Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 梶山 公則、古賀 義則: "心肥大とカテコールアミン受容体:α受容体とβ受容体の細胞内情報伝達機構" 医学のあゆみ. 154. 757- (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] 辻 ゆかり、梶山 公則、古賀 義則 他: "自然発症高血圧ラットにおける心筋内カテコールアミンと細胞内情報伝達系の検討" 心臓. 23(supp12). 11-14 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 古賀 義則、大月 務、岡 直樹: "心肥大形成のメカニズム2 液性因子による心肥大" 治療学. 26. 1445-1449 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakata M,chiba M,Koga Y et al: "Predominant expression of skeletal α-actin m-RNA in the left ventricular endocardium and apex at the early stage of pressure overload" Circulation. 84. 2-49 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Koga Y,Iwami G, Nakata M et al: "Adrenergic and angiotensin systems in cardiuc bypertrophy" J Mol Cell Cardiol. 24. 1-41 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Iwami G,Tsuji Y, Koga Y et al: "Activation of PKC and IP_3 during pressure overlood by antic constriction in spontunecusly hypertensive vats" J Mol Cell Cardiol. 24. 1-61 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 古賀 義則、戸嶋 裕徳: "心・血管系におけるα受容体 心肥大におけるアドレナリン受容体の役割" Excerptu Medica 東京, 11-26 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] 古賀 義則、梶山 公則: "心不全 心肥大2心不全" 南江堂、東京, 262-268 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 辻 ゆかり: "自然発症高血圧ラットにおける心筋内カテコ-ルアミンと細胞内情報伝達系の検討" 心臓. 23(Suppl 2). 11-14 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 梶山 公則: "心肥大とカテコ-ルアミン受容体" 医学のあゆみ. 154. 757 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 辻 ゆかり: "自然発症高血圧ラットにおける心筋内カテコラミンと細胞内情報伝達系の検討" 心臓.

    • Related Report
      1990 Annual Research Report
  • [Publications] 古賀 義則: "心血管系におけるα受容体(心肥大におけるアドレナリン受容体の役割)" Excerpta Medica, 11-26 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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