Role of If channel remodeling in atrial fibrillation appearance in diabets

• Project/Area Number: 23790249
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Oita University
• Principal Investigator: TETSUJI SHINOHARA 大分大学, 医学部, 助教 (60457629)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 洞房結節 / 心房細動 / 糖尿病 / 洞不全症候群 / インスリン抵抗性 / Leptin / Atrial fibrillation / Atrial fibrosis

Research Abstract

Both the membrane clock and the Ca2+ clock are important in the initiation of the heart beat, and malfunction of these two clocks leads to sinoatrial node (SAN) dysfunction. SAN function and arrhythmic events were evaluated in 14 weeks old male hereditary insulin-resistant Otsuka Long-Evans Tokushima fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. OLETF rats showed longer correct sinus node recovery time. The mRNA levels of HCN4, RyR2, and phospholamban were downregulated in OLETF rats compared with LETO rats (p<0.01). SAN dysfunction in insulin-resistant rats was associated with malfunction of both membrane clock and Ca clock.

Research Products

• [Journal Article] Combination therapy of cilostazol and bepridil suppresses recurrent ventricular fibrillation related to J-wave syndromes (2014)
  • Author(s): Shinohara T, Ebata Y, Ayabe R, Fukui A, Okada N, Yufu K, Nakagawa M, Takahashi N
  • Journal Title: Heart Rhythm Volume: (in press)
• [Journal Article] Carvedilol analog modulates both basal and stimulated sinoatrial node automaticity (2014)
  • Author(s): Shinohara T, Kim D, Joung B, Maruyama M, Vembaiyan K, Back TG, Wayne Chen SR, Chen PS, Lin SF
  • Journal Title: Heart Vessels Volume: 29 Pages: 396-403
• [Journal Article] Role of leptin signaling in the pathogenesis of angiotensin II-mediated atrial fibrosis and fibrillation (2013)
  • Author(s): Fukui A, Takahashi N, Nakada C, Masaki T, Kume O, Shinohara T, Teshima Y, Hara M, Saikawa T
  • Journal Title: Circ Arrhythm Electrophysiol Volume: 6 Pages: 402-409
• [Journal Article] Role of Leptin Signaling in the Pathogenesis of Angiotensin II-Mediated Atrial Fibrosis and Fibrillation. (2013)
  • Author(s): Fukui A, Takahashi N, Nakada C, Masaki T, Kume O, Shinohara T, Teshima Y, Hara M, Saikawa T.
  • Journal Title: Circ Arrhythm Electrophysiol Volume: 2 Issue: 2 Pages: 402-9
  • DOI: 10.1161/circep.111.000104
  • Peer Reviewed
• [Journal Article] Carvedilol analog modulates both basal and stimulated sinoatrial node automaticity. (2013)
  • Author(s): Shinohara T, Kim D, Joung B, Maruyama M, Vembaiyan K, Back TG, Wayne Chen SR, Chen PS, Lin SF.
  • Journal Title: Heart Vessels Volume: 0 Issue: 3 Pages: 0-0
  • DOI: 10.1007/s00380-013-0378-2
  • Peer Reviewed
• [Presentation] Hyperleptinemia Exacerbates High Fat Diet-mediated Atrial Remodeling and Fibrillation (2014)
  • Author(s): Fukui A, Kondo H, Saito S, Nishi S, Shinohara T, Teshima Y, Saikawa T, Takahashi N
  • Organizer: 日本循環器学会総会学術集会
  • Place of Presentation: 東京
• [Presentation] Role of Spleen-Derived Interleukin-10 in High-Fat-Diet-Induced Inflammatory Atrial Fibrosis and Fibrillation (2014)
  • Author(s): Kondo H, Takahashi N, Saito S, Fukui A, Nishio S, Aoki K, Shinohara T, Teshima Y, Hara M, Saikawa T
  • Organizer: 日本循環器学会総会学術集会
  • Place of Presentation: 東京
• [Presentation] Interleukin-10 Treatment Attenuayes Sinus Node Dysfunction and Atrial Fibrillation Vulnerability Caused by Streptozotocin-Induced Hyperglycemia (2014)
  • Author(s): Kondo H, Saito S, Fukui A, Nishio S, Shinohara T, Teshima Y, Takahashi N
  • Organizer: 日本循環器学会総会学術集会
  • Place of Presentation: 東京
• [Presentation] Insulin-resistance modulate both Membrane clock and Ca2+ clock leading to sinus node dysfunction (2014)
  • Author(s): Fukui A, Shinohara T, Takahashi N, Kondo H, Saito S, Teshima Y, Hara M, Saikawa T
  • Organizer: 日本循環器学会総会学術集会
  • Place of Presentation: 横浜
• [Presentation] Role of Leptin Signaling in Pathogenesis of Atrial Fibrosis and Fibrillation (2014)
  • Author(s): Fukui A, Takahashi N, Shinohara T, Saikawa T
  • Organizer: 日本循環器学会総会学術集会
  • Place of Presentation: 福岡
• [Presentation] Interleukin-10 Treatment Attenuates Sinus Node Dysfunction and Atrial Fibrillation Vulunerability Caused by Streptozotocin-Induced Hyperglycemia (2014)
  • Author(s): Kondo H et al.
  • Organizer: 日本循環器学会総会学術集会
  • Place of Presentation: 東京
• [Presentation] Insulin-resistance modulate both Membrane clock and Ca2+ clock leading to sinus node dysfunction (2013)
  • Author(s): Fukui A, Takahashi N, Saito S, Nishio S, Teshima Y, Saikawa T
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Role of Leptin Signaling in Pathogenesis of Atrial Fibrosis and Fibrillation (2012)
  • Author(s): Fukui A, Takahashi N, Shinohara T, Saikawa T, et al.
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡