The role of salt sensitivity in the development of heart failure with preserved ejection fraction and the relation of intrinsic steroids

• Project/Area Number: 21590893
• 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: Osaka University
• Principal Investigator: SAKATA Yasushi 大阪大学, 医学系・研究科, 講師 (00397671)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Kazuhiro 鳥取大学, 医学部, 教授 (90303966) ; MANO Toshiaki 大阪大学, 医学部附属病院, 講師 (90379165)
• 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 心不全 / 拡張機能 / 食塩感受性 / 内因性ステロイド

Research Abstract

The production of CTS was enhanced in hypertensive HFPEF model. Ouabain activated p42/ 44 MAPKs and enhanced collagen production through the elevation of cytosolic Ca^<2+> concentration via NCX entry mode. SEA0400, the potent inhibitor of NCX entry mode, prevented the development of LV fibrosis and stiffening and the transition to HFPEF with the improvement of survival rate in the animal models. Thus, CTS and the subsequently activated Ca^<2+> entry mode of NCX may play an important role in the development of LV fibrosis and hypertensive HFPEF, and the blockade of the entry mode of NCX is likely a new therapeutic strategy for this phenotype of heart failure.

Research Products

• [Journal Article] Ca2+ Entry Mode of Na+/ Ca2+ Exchanger as A New Therapeutic Target for Heart Failure with Preserved Ejection Fraction (2011)
  • Author(s): Kamimura D, Ohtani T, Sakata Y, Mano T, Tkaeda Y, Tamaki S, Omori Y, Tshkamoto Y, Furutani K, Komiyama Y, Yoshika M, Takahashi H, Matsuda T, Baba A, Umemura S, Miwa T, Komuro I, Yamamoto K.
  • Journal Title: Eur Heart J Volume: (in press)
  • Peer Reviewed
• [Journal Article] Ca2+ entry mode of Na+/Ca2+ exchanger as a new therapeutic target for heart failure with preserved ejection fraction (2011)
  • Author(s): Kamimura D, Ohtani T, Sakata Y, Mano T, Takeda Y, Tamaki S, Omori Y, Tsukamoto Y, Furutani K, Komiyama Y, Yoshika M, Takahashi H, Matsuda T, Baba A, Umemura S, Miwa T, Komuro I, Yamamoto K
  • Journal Title: European Heart Journal Volume: (In press)
  • Peer Reviewed
• [Journal Article] Long-term beta-blocker therapy improves diastolic function even without the therapeutic effect on systolic function in patients with reduced ejection fraction (2010)
  • Author(s): Tamaki S, Sakata Y, et al
  • Journal Title: J Cardiol Volume: 56 Pages: 176-182
  • Peer Reviewed
• [Journal Article] Noninvasive Assessment of Wall Distensibility with the Evaluation of Diastolic Epicardial Movement (2009)
  • Author(s): Takeda Y, Sakata Y, et al
  • Journal Title: J Card Fail 15 Pages: 68-68
  • Peer Reviewed
• [Journal Article] Heart Failure with Preserved Ejection Fraction (2009)
  • Author(s): Yamamoto K, Sakata Y, et al
  • Journal Title: Circ J 73 Pages: 404-404
  • Peer Reviewed
• [Journal Article] Competing risks of heart failure with preserved ejection fraction in diabetic patients
  • Author(s): Takeda Y, Sakata Y, et al
  • Journal Title: Eur J Heart Fail Volume: (In press)
  • Peer Reviewed
• [Presentation] Diastolic Wall Strain Reflects the Myocardial Fibrosis in Heart Transplanted Patients (2009)
  • Author(s): Sakata Y, et al
  • Organizer: American Heart Association
  • Place of Presentation: Orlando, Flo, USA
  • Year and Date: 2009-11-15