Basic study of regression of hypertensive myocardial fibrosis andthe development of treatment strategies

• Project/Area Number: 19590813
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Mie University
• Principal Investigator: YOSHIDA Kyoko Mie University, 大学院・医学系研究科, 准教授 (00242967)
• Co-Investigator(Kenkyū-buntansha): ONISHI Katsuya 三重大学, 大学院・医学系研究科, 助教 (40343222)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 心臓 / 線維化 / 高血圧 / 細胞外基質 / テネイシン / 心肥大 / マウス

Research Abstract

高血圧心では、心筋細胞肥大とともに間質に線維化が見られ心機能不全の原因となるが、治療開始する際、患者はある程度の罹病期間を経て線維化病変が形成されている。本研究では、マウス高血圧モデルを用い、すでに出来上がった線維化病変が可逆的かどうかを検討した。高血圧による心筋細胞肥大は比較的早期に回復しうるが、一度形成された間質線維化病変の消褪には、何らかの積極的治療を行わなければ長い時間を必要とすることが示唆された。

Research Products

• [Journal Article] High prevalence of chronic myocarditis in dilated cardiomy opathy referred for left ventriculoplasty : Expression of tenascin-C as a possible marker for inflammation. (2009)
  • Author(s): Tsukada B, et al
  • Journal Title: Human Pathol (印刷中)
  • Peer Reviewed
• [Journal Article] Stromal tenascin-C regulates epithelial cell differentiationin mouse prostate (2008)
  • Author(s): Ishii,K., Imanaka-Yoshida K., YoshidaT, Sugimura Y.
  • Journal Title: Dev Biol 324 Pages: 310-9
  • Peer Reviewed
• [Journal Article] Noninvasive detection of cardiac repairafter acute myocardial infarction in ratsby 111 In Fab fragment of monoclonalantibody specific for tenascin-C (2008)
  • Author(s): Odaka K., Uehara T., Arano Y., AdachiS, Tadokoro H., Yoshida K., Hasegawa H,Imanaka-Yoshida K.., Yoshida T., HiroeM., Irie T, Tanada S, Komuro I.
  • Journal Title: Int Heart J 49 Pages: 481-92
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid tenascin-Cincreases preceding the development ofchronic shunt-dependent hydrocephalusafter subarachnoid hemorrhage (2008)
  • Author(s): Suzuki H., Kinoshita N.,Imanaka-Yoshida K.,Yoshida T., TakiW
  • Journal Title: Stroke 39 Pages: 1610-2
  • Peer Reviewed
• [Journal Article] Basic fibroblast growth factor slow releasestent graft for endovascular aorticaneurysm repair : a canine model experiment (2008)
  • Author(s): Kajimoto M., Shimono T., Hirano K,Miyake Y., Kato N, Imanaka-Yoshida K,Shimpo H and Miyamoto K.
  • Journal Title: J Vasc Surg 48 Pages: 1306-14
• [Journal Article] Atrial natriuretic peptide genetransfection with a novel envelope vectorsystem ameliorates pulmonary hypertensionin rats (2008)
  • Author(s): Mitani, Y., Maruyama, J., Jiang, B.H., Sawada, H., Shimpo, H., Imanaka-Yoshida, K., Kaneda, Y., Komada, Y., and Maruyama, K.
  • Journal Title: J Thorac Cardiovasc Surg 136 Pages: 142-9
• [Journal Article] テネイシンC (2008)
  • Author(s): 今中恭子、廣江道昭、吉田利通
  • Journal Title: Heart View 8 Pages: 124-129
• [Journal Article] テネイシンCの心臓リモデリングにおける有用性 (2008)
  • Author(s): 廣江道昭、今中(吉田)恭子、吉田利通
  • Journal Title: 医学の歩み 224 Pages: 408-413
• [Journal Article] 組織リモデリングにおけるテネイシンの役割 (2008)
  • Author(s): 吉田利通、石垣共基、今中-吉田恭子
  • Journal Title: 生体の科学 591 Pages: 123-128
• [Journal Article] Conventional therapy with an ACE inhibitor diminishes left ventricular dyssynchrony during the progression of heart failure. (2008)
  • Author(s): Kurita T, et al
  • Journal Title: Int J Cardiol (印刷中)
  • Peer Reviewed
• [Journal Article] Noninvasive detection of cardiac repair after acute myocardial infarction in rats by 111 In Fab fragment of monoclonal antibody specific for tenascin-C. (2008)
  • Author(s): Odaka, K, et al
  • Journal Title: Int Heart J 49 Pages: 481-492
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid tenascin-C increases preceding the development of chronic shunt-dependent hydrocephalus after subarachnoid hemorrhage. (2008)
  • Author(s): Suzuki H, et al
  • Journal Title: Stroke 39 Pages: 1610-1612
  • Peer Reviewed
• [Journal Article] Th1-type immuneresponses by Toll-like receptor 4signaling are required for the developmentof myocarditis in mice with BCG-inducedmyocarditis (2007)
  • Author(s): Nishikubo, K., Imanaka-Yoshida, K.,Tamaki, S., Hiroe, M., Yoshida, T., Adachi,Y., Yasutomi, Y.
  • Journal Title: J Autoimmun 29 Pages: 146-53
  • Peer Reviewed
• [Journal Article] Expression of large tenascin-C splicevariants by hepatic stellatecells/myofibroblasts in chronic hepatitis C (2007)
  • Author(s): El-Karef, A., Kaito, M., Tanaka, H.,Ikeda, K., Nishioka, T., Fujita, N., Inada,H., Adachi, Y., Kawada, N., Nakajima, Y.,Imanaka-Yoshida, K., and Yoshida, T.
  • Journal Title: J Hepatol 46 Pages: 664-73
  • Peer Reviewed
• [Journal Article] Eplerenone attenuates myocardial fibrosisin the angiotensin II-induced hypertensivemouse: involvement of tenascin-C inducedby 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 49 Pages: 261-8
  • Peer Reviewed
• [Journal Article] Tenascin-Csynthesized in both donor grafts andrecipients accelerates artery graftstenosis (2007)
  • Author(s): Sawada, Y., Onoda, K., Imanaka-Yoshida,K., Maruyama, J., Yamamoto, K., Yoshida, T., and Shimpo, H.
  • Journal Title: Cardiovasc Res 74 Pages: 366-76
  • Peer Reviewed
• [Journal Article] Higher serum tenascin-C levels reflect theseverity of heart failure, leftventricular dysfunction and remodeling inpatients 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., and Kitabatake, A.
  • Journal Title: Circ J 71 Pages: 327-30
  • Peer Reviewed
• [Journal Article] Locally appliedcilostazol suppresses neointimalhyperplasia and medial thickening in a veingraft model (2007)
  • Author(s): Yamamoto K., Onoda K., Sawada Y., Fujinaga, K, Imanaka-Yoshida K., Yoshida T, and Shimpo H.
  • Journal Title: Ann Thorac Cardiovasc Surg 13 Pages: 322-30
  • Peer Reviewed
• [Journal Article] Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse:involvement of tenascin-C induced by aldosterone-mediated inflammation. (2007)
  • Author(s): Nishioka, T, Suzuki M, Onishi K, T akakura N, Inada H, Yoshida T, Hiroe M, Imanaka-Yoshida K.
  • Journal Title: J Cardiovasc Pharmacol 49 Pages: 261-268
  • Peer Reviewed
• [Journal Article] Higher serum tenascin-C levels reflect the severity of heart failure, left venr dysfunction afnd remodeling in patients with dilated cardiomyopathy (2007)
  • Author(s): Terasaki, , Imanaka-Ybshida K, (他9名)
  • Journal Title: Circ J 71 Pages: 327-330
  • Peer Reviewed
• [Journal Article] Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatihs in mice (2007)
  • Author(s): EI-Karef, A, Imanaka-Ybshida K, 他5名)
  • Journal Title: J Pathol 211 Pages: 86-94
  • Peer Reviewed
• [Journal Article] High prevalence of chronicmyocarditis in dilated cardiomyopathyreferred for left ventriculoplasty:Expression of tenascin-C as a possiblemarker for inflammation
  • Author(s): Tsukada B, Terasaki F, Shimomura H,Otsuka K, Otsuka K, Katashima T, Fujita S,Imanaka-Yoshida K , Yoshida T, Hiroe M, and Kitaura Y
  • Journal Title: Human Pathol (in press)
  • Peer Reviewed
• [Journal Article] Conventionaltherapy with an ACE inhibitor diminishesleft ventricular dyssynchrony during theprogression of heart failure
  • Author(s): Kurita T, Onishi K, Dohi K, Takamura T,Fujimoto N, Tanigawa T, Imanaka-Yoshida K,Wada H, Nobori T, Ito M
  • Journal Title: Int J Cardiol (in press)
  • Peer Reviewed
• [Presentation] Incrementalprognostic values of serum tenascin-Clevels to late gadolinium enhancement bycardiac magnetic resonance in patientswith dilated cardiomyopathy (2009)
  • Author(s): Kurita T, Onishi K, Sakuma H, Nakajima1.H, Fujimoto N, Ishida N, Dohi K, OkamotoS, Imanaka-Yoshida K, Ito M.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-22
• [Presentation] Incremental prognostic values of serum tenascin-C levels to late gadolinium enhancement by cardiac magnetic resonance in patients with dilated cardiomyopathy (2009)
  • Author(s): Kurita T, et al
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-22
• [Presentation] Tenascin-C may play asignificant role in maturation of coronaryarteries in mouse (2008)
  • Author(s): Imanaka-Yoshida K, Hara M, Namikata M,Yoshida T, Schwartz RJ, Hiroe M,Miyagawa-Tomita S.
  • Organizer: Weinstein Cardiovascular Development Conference
  • Place of Presentation: Houston, Texas, USA
• [Presentation] Deletionof Tenascin-C prevents left ventricularremodeling and cardiac failure aftermyocardial infarction (2008)
  • Author(s): Imanaka-Yoshida K, Nishioka T, OnishiK, Tsutsui H, Yoshida T, Hiroe M.
  • Organizer: Basic Cardiovascular Science Conference 2008
  • Place of Presentation: Keystone Colorado, USA
• [Presentation] Imanaka-Yoshida K.Incremental value of tenascin-C andBNP leels for predicting prognosis inpatients with dilated cardiomyopathyand decompensated heart failure (2008)
  • Author(s): Hiroe M, Onishi K, Fujimoto N, SatoA, Yoshida T.
  • Organizer: Basic Cardiovascular Science Conference 2008
  • Place of Presentation: Keystone Colorado, USA
• [Presentation] Tenascin-C inducesepitheial-mesenchymal transition likechange through recruitment of ・v・6integrin and phosphorylation of focaladhesion kinase by sec in breast cancercells (2008)
  • Author(s): Yoshida T, Nagaharu K,Imanaka-Yoshida K.
  • Organizer: The American Society for CellBiology 48th Annual Meeting
  • Place of Presentation: San Francisco CA, USA
• [Presentation] Tenascin-C mayaccelerate adverse cardiac remodeling andcardiac failure (2008)
  • Author(s): Imanaka-Yoshida K., Nishioka T, NaganoY., Onishi K, Yoshida T.
  • Organizer: The American Societyfor Cell Biology 48th Annual Meeting
  • Place of Presentation: San Francisco CA, USA
• [Presentation] Tenascin-Cpromotes cardiacremodeling and hypertrophy duringmyocardial repair (2008)
  • Author(s): Imanaka-Yoshida K, Onishi K, TsutsuiH,. Hiroe M.
  • Organizer: 第71回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡
• [Presentation] Serum tenascin-C is a novel surrogate forassessing the severity of heart failure,ventricular remodeling and prognosis ofdilated cardiomyopathy (2008)
  • Author(s): Terasaki F, Kitaura Y, Onishi K, SatoA, Hiroe M, Imanaka-Yoshida K, Yoshida T.
  • Organizer: 第71回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡
• [Presentation] Tenascin-C may accelerate adverse cardiac remodeling and cardiac failure. (2008)
  • Author(s): Imanaka-Yoshida K, et al
  • Organizer: The American Society for Cell Biology 48th Annual Meeting
  • Place of Presentation: San Francisco CA, USA
• [Presentation] Deletion of Tenascin-C prevents left ventricular remodeling and cardiac failure after myocardial infarction. (2008)
  • Author(s): Imanaka-Yoshida K, et al
  • Organizer: Basic Cardiovascular Science Conference 2008
  • Place of Presentation: Keystone Colorado, USA
• [Presentation] Incremental value of tenascin-C and BNP leels for predicting prognosis in patients with dilated cardiomyopathy and decompensated heart failure. (2008)
  • Author(s): Hiroe M, et al
  • Organizer: Basic Cardiovascular Science Conference 2008
  • Place of Presentation: Keystone Colorado, USA
• [Presentation] 高血圧性心筋線維化病変は可逆性か (2007)
  • Author(s): 田中 裕子、吉田 利通、今中・吉田 恭子
  • Organizer: 第96回日本病理学会
  • Place of Presentation: 大阪市
  • Year and Date: 2007-03-13
• [Presentation] テネイシンC 過剰発現マウスの作製とそれを用いた組織傷害モデルでの解析 (2007)
  • Author(s): 飛田理世, 長野由佳, 西岡朋弘, 吉田利通, 今中恭子
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪
• [Presentation] 高血圧性心筋線維化病変は可逆性か (2007)
  • Author(s): 田中裕子, 吉田利通, 今中-吉田恭子
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪