Novel Strategy to prevent ischemia/reperfusion injury that overcomes disadvantages of antioxidant agents

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592672
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Oita University
• Principal Investigator: TAKAHASHI NAOHIKO 大分大学, 医学部, 教授 (30263239)
• Co-Investigator(Kenkyū-buntansha): TESHIMA Yasushi 大分大学, 医学部, 助教 (10457608) ; HAGIWARA Satoshi 大分大学, 医学部, 講師 (50527661) ; SAIKAWA Tetsunori 大分大学, 医学部, 教授 (60145365) ; NOGUCHI Takayuki 大分大学, 医学部, 教授 (90156183)
• Project Period (FY): 2011 – 2013
• Keywords: 心房細動 / メタボリック症候群

Research Abstract

We examined the hypothesis that leptin signaling contributes to the atrial fibrosis and atrial fibrillation (AF) evoked by angiotensin II (AngII). Male CL57/B6 (CNT) and leptin-deficient ob/ob mice (Ob) were subcutaneously infused with AngII. In CNT-AngII mice, leptin expression in the left atrium was upregulated. Transesophageal burst pacing induced AF in 88% of CNT-AngII mice, but not in Ob-AngII mice (0%). In isolated perfused hearts, AF was induced only in CNT-AngII mice (67%). Inter-atrial conduction time was prolonged in CNT-AngII mice, but not in Ob-AngII mice. In cultured SD rat atrial fibroblasts, AngII treatment increased leptin expression. Addition of leptin increased TGF-beta1, alpha-SMA, MCP-1 and RANTES expressions in SD rat atrial fibroblasts but not in Zucker rat atrial fibroblasts. These observations demonstrate that leptin signaling is essential for the development of atrial fibrosis and AF evoked by AngII.

Research Products

• [Journal Article] Production of reactive oxygen species in the diabetic heart. Roles of mitochondria and NADPH oxidase (2014)
  • Author(s): Teshima Y, Takahashi N, Nishio S, Saito S, Kondo H, Fukui A, Aoki K, Yufu K, Nakagawa M, Saikawa T
  • Journal Title: Circ J Volume: 78(2) Pages: 300-306
• [Journal Article] Role of leptin signaling in the pathogenesis of angiotensin II-mediated atrial fibrosisand 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(2) Pages: 402-409
• [Presentation] Takahashi N. Hyperleptinemia exacerbates high fat diet-mediated atrial remodeling and fibrillation (2014)
  • Author(s): Fukui A, Kondo H, Saito S, Nishio S, Shinohara T, Teshima Y, Saikawa T
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23
• [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: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23
• [Presentation] Interleukin-10 treatment attenuates 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: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23
• [Presentation] Glucose fluctuations aggravate atrial fibrillation in animal models of Type 1 and Type 2 diabetes mellitus (2014)
  • Author(s): Saito S, Teshima Y, Nishio S, Kondo H, Fukui A, Nakagawa M, Saikawa T, Takahashi N
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23
• [Presentation] Role of indoxyl sulfate, a major uremic toxin, in pathogenesis of atrial fibrillation associated with chronic kidney disease (2014)
  • Author(s): Aoki K, Takahashi N, Kondo H, Saito S, Nishio S, Fukui A, Shinohara T, Teshima Y, Shibata T
  • Organizer: 第78回日本循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20140321-23