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A study for prevention of ventricular remodeling after myocardial infarction by regulating functions of tenascin-C.

Research Project

Project/Area Number 17590724
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionMie University

Principal Investigator

YOSHIDA Kyoko  Mie University, Graduate School of Medicine, Department of Pathology and Matrix Biology, Research Professor, 大学院医学系研究科, 助教授 (00242967)

Co-Investigator(Kenkyū-buntansha) ONISHI Katsuya  Mie University, Graduate School of Medicine, Department of Laboroatory Medicine, Assistant Professor, 大学院医学系研究科, 助手 (40343222)
HARA Mari  Mie University, Graduate School of Medicine, Department of Pathology and Matrix Biology, Research Associate, 大学院医学系研究科, 教務職員 (30176383)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordstenascin / extracellular matrix / knockout mouse / transgenic mouse / myocardial infarction / ventricular remodeling
Research Abstract

Tenascin-C (TN-C), an extracellular matrix glycoprotein, transiently appears in the pathologic heart, playing important roles in tissue remodeling. To elucidate its role in ventricular remodeling after acute myocardial infarction(AMI), we measured TN-C levels in patients with AMI and compared with cardiac function and patient outcomes. Serum TN-C levels were significantly elevated during the acute stage after AMI and peaked within 5 days. Peak TN-C levels were significantly higher in the left ventricular (LV) remodeling group than the non-remodeling group. AMI patients with high TN-C levels were at much higher risk of cardiac death, non fatal AMI, and hospitalization for congestive heart failure. Next, we examined the effects of deletion of TN-C on post-AMI ventricular remodeling using TN-C knockout(KO) mice and compared with those of the wild type(WT). Although no significant difference was detected in survival rate between KO and WT by day 28, The KO mice exerted significantly less LV cavity dilatation, less elevation of endodiastolic left ventricular pressure, and improved fractional shortening and ejection fraction. Histologically, interstitial fibrosis in the residual myocardium is reduced in KO mice. Furthermore, we examined myocardial repair after injury in heart specific TN-C over-expressing mice using a mouse genetic system based on Cre/loxP recombination. With excess expression of TN-C, recruitment of myofibroblasts and myocardial fibrosis was accelerated to compared with that in WT. Although the effects of TN-C on ventricular remodeling are not simple, but rather are bidirectional, it was suggested that excessive and sustained increments of TN-C could inappropriate reconstruction of infarcted ventricular wall and a potential therapeutic target.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (30 results)

All 2007 2006 2005 Other

All Journal Article (30 results)

  • [Journal Article] Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse : involvement of tenascin-C induce by aldosterone-mediated inflammation.2007

    • Author(s)
      Nishioka T(他6名), Imanaka-Yoshida K
    • Journal Title

      Journal of Cardiovasccular Pharmacology (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Tenascin-C synthesized in both donor grafts and recipients accelerates artery graft stenosis2007

    • Author(s)
      Sawada Y, Onoda K, Imanaka-Yoshida K(他4名)
    • Journal Title

      Cardiovascular Research (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Higher serum tenascin-C levels reflect the severity of heart failure, left ventricular dysfunction and remodeling in patients with dilated cardiomyopathy.2007

    • Author(s)
      Terasaki F, Onishi K, Imanaka-Yoshida K(他8名)
    • Journal Title

      Circulation Journal 71

      Pages: 327-330

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] テネイシンーC2007

    • Author(s)
      廣江道昭, 今中-吉田恭子, 吉田利通
    • Journal Title

      日本臨床 心不全 (上) (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatitis in mice.2007

    • Author(s)
      El-Karef A(他5名), Imanaka-Yoshida K
    • Journal Title

      Journal of Pathology 211

      Pages: 86-94

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse : involvement of tenascin-C induce by aldosterone-mediated inflammation.2007

    • Author(s)
      Nishioka T, Suzuki M, Onishi K, Takakura N, Inada H, Yoshida T, Hiroe M, Imanaka-Yoshida K.
    • Journal Title

      J Cardiovasc Pharmacol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Higher serum tenascin-C levels reflect the severity of heart failure, left ventricular dysfunction and remodeling in patients with dilated cardiomyopathy.2007

    • Author(s)
      Terasaki F, Okamoto H, Onishi K, Sato A, Shimomura H, Tsukada B, Imanaka-Yoshida K, Hiroe M, Yoshida T, Kitaura Y, Kitabatake A
    • Journal Title

      Circ J 71

      Pages: 327-330

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatitis in mice.2007

    • Author(s)
      E1-Karef A, Yoshida T, Gabazza EC, Nishioka T, Inada H, Sakakura T, Imanaka-Yoshida K.
    • Journal Title

      J Pathol 211

      Pages: 86-94

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] テネイシンーC2007

    • Author(s)
      廣江道昭, 今中-吉田恭子, 吉田利通
    • Journal Title

      日本臨床 心不全(上) (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Tenascin-C synthesized in both donor grafts and recipients accelerates artery graft stenosis2007

    • Author(s)
      Sawada Y, Onoda K, Imanaka-Yoshida K(他4名)
    • Journal Title

      Circulation Journal 71

      Pages: 327-330

    • Related Report
      2006 Annual Research Report
  • [Journal Article] In vitro model for mouse coronary vasculogenesis.2006

    • Author(s)
      Watanabe N, Hara M(他4名), Imanaka-Yoshida K
    • Journal Title

      Anatomical Record 288A

      Pages: 714-722

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse.2006

    • Author(s)
      Nakahara H, Imanaka-Yoshida K(他13名)
    • Journal Title

      European Journal of Immunology 36

      Pages: 3334-3345

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A crucial role of mitochondrial Hsp40 in preventing dilated cardiomyopathy.2006

    • Author(s)
      Kajimoto M, Imanaka-Yoshida K(他10名)
    • Journal Title

      Circulation 114

      Pages: 1378-1383

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] A crucial role of mitochondrial Hsp40 in preventing dilated cardiomyopathy.2006

    • Author(s)
      Hayashi M, Imanaka-Yoshida K(他5名)
    • Journal Title

      Nature Medicine 12

      Pages: 128-132

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 心血管リモデリングとテネイシンC.2006

    • Author(s)
      今中-吉田恭子
    • Journal Title

      分子心血管病 7

      Pages: 265-271

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] In vitro model for mouse coronary vasculogenesis.2006

    • Author(s)
      Watanabe N, Nakagawa M, Hanato T, Takeuchi Y, Hara M, Yoshida T, Imanaka-Yoshida K
    • Journal Title

      Anat Rec A Discov Mol Cell Evol Biol 288A

      Pages: 714-722

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Serum tenascin-C might be a novel predictor of left ventricular remodeling and prognosis after acute myocardial infarction.2006

    • Author(s)
      Sato A, Aonuma K, Imanaka-Yoshida K, Yoshida T, Isobe M, Kawase D, Kinoshita N, Yazaki Y, Hiroe M.
    • Journal Title

      J Am Coll Cardiol 47

      Pages: 2319-2325

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Imanaka-Yoshida K, Suzuki K, Yoshida T, Adachi Y, Taguchi O. Deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse.2006

    • Author(s)
      Nakahara H, Gabazza EC, Fujimoto H, Nishii Y, D'Alessandro-Gabazza CN, Bruno NE, Takagi T, Hayashi T, Maruyama J, Maruyama K
    • Journal Title

      Eur J Immunol 36

      Pages: 3334-3345

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A crucial role of mitochondrial Hsp40 in preventing dilated cardiomyopathy.2006

    • Author(s)
      Hayashi M, Imanaka-Yoshida K, Yoshida T, Wood M, Fearns C, Tatake RJ, Lee JD
    • Journal Title

      Nat Med 12

      Pages: 128-132

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A crucial role of mitochondrial Hsp40 in preventing dilated cardiomyopathy.2006

    • Author(s)
      Hiayashi M, Imanaka-Yoshida K(他5名)
    • Journal Title

      Nature Medicine 12

      Pages: 128-132

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Serum Tenascin-C might be a Novel Predictor of Left Ventricular Remodeling and Prognosis after Acute Myocardial Infarction.2006

    • Author(s)
      Sato A, Aonuma K, Imanaka-Yoshida K他6名
    • Journal Title

      Journal-of American College of Cardiology (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tenascin-C coated on platinum coils for acceleration of organization of cavities and reduction of lumen size in a rat aneurysm model.2005

    • Author(s)
      Toma N, Imanaka-Yoshida K, Takeuchi T, Matsushima S, Iwata H, Yoshida T, Taki W.
    • Journal Title

      J Neurosurg 103

      Pages: 681-686

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tenascin-C regulates recruitment of myofibroblasts during tissue repair after myocardial injury.2005

    • Author(s)
      Tamaoki M, Imanaka-Yoshida K, Yokoyama K, Nishioka T, Inada H, Hiroe M, Sakakura T, Yoshida T.
    • Journal Title

      Am J Pathol 167

      Pages: 71-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Method of cell transplantation promoting the organization of intraarterial thrombus.2005

    • Author(s)
      Hirano K, Shimono T, Imanaka-Yoshida K, Miyamoto K, Fujinaga K, Kajimoto M, Miyake Y, Nishikawa M, Yoshida T, Uchida A, Shimpo H, Yada I, Hirata H.
    • Journal Title

      Circulation 112

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tenascin-C regulates recruitment of myofibroblasts during tissue repair after myocardial injury.2005

    • Author(s)
      Tamaoki M, Imanaka-Yoshida K, Yokoyama K他6名
    • Journal Title

      American Joural of Pathology 167

      Pages: 71-80

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Method of cell transplantation promoting the organization of ntraarterial thrombus.2005

    • Author(s)
      Hirano K, Shimono T, Imanaka-Yoshida K, 他10名
    • Journal Title

      Circulation 112

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Diagnostic utility of tenascin-C for evaluation of the activity of human acute myocarditis.2005

    • Author(s)
      Morimoto S, Imanaka-Yoshida K, 他10名
    • Journal Title

      Journal of Pathology 205

      Pages: 460-467

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tenascin-C is an essential factor for neointimal hyperplasia after aortotomy in mice.2005

    • Author(s)
      Yamamoto K, Onoda K, Sawada Y, Fujinaga K, Imanaka-Yoshida K他3名
    • Journal Title

      Cardiovascular Research 65

      Pages: 737-742

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tenascin-C coated on platinum coils for acceleration of organization of cavities and reduction of lumen size in a rat aneurysm model.2005

    • Author(s)
      Toma N, Imanaka-Yoshida K, Takeuchi T他5名
    • Journal Title

      Journal of Neurosurgery 103

      Pages: 681-686

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Tenascin-C synthesized in both donor grafts and recipients accelerates artery graft stenosis.

    • Author(s)
      Sawada Y, Onoda K, Imanaka-Yoshida K, Maruyama J, Yamamoto K, Yoshida T, Shimpo H
    • Journal Title

      Cardiovasc Res (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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