Functional Analysis of Dendritic Cells in the Pathophysiology of Heart Failure and a Study of Heart Failure Treatment Targeting Dendritic Cells

• Project/Area Number: 22790739
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kurume University
• Principal Investigator: SUGI Yusuke 久留米大学, 医学部, 助教 (40389250)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 循環器 / 心不全 / 免疫学 / 心筋障害 / 樹状細胞 / 自己免疫 / statin

Research Abstract

We focused on dendritic cells(DCs) which are the most potent antigen-presenting cells. We demonstrated that the numbers and activation markers of DCs were correlated with cardiac function, clinical parameters and prognosis in patients with decompensated heart failure. We also investigated whether DCs would be involved in the pathogenesis of heart failure using mice myocarditis model. Autoimmune myocarditis and heart failure were induced by DCs pulsed with cardiac antigen peptide. These autoimmune myocarditis and heart failure were attenuated by simvastatin. We also examined the effects of simvastatin on activation markers and cytokines production of DCs in vitro. Simvastatin significantly suppressed activation markers and inflammatory cytokines. These results suggest that DCs may play a role in the pathogenesis of heart failure and simvastatin may suppress dendritic cell-induced autoimmune myocarditis, possibly by inhibiting the activation and inflammatory cytokines production of DCs.

Research Products

• [Journal Article] Reduction and activation of circulating dendritic cells in patients with decompensated heart failure (2011)
  • Author(s): Sugi Y, Yasukawa H, Kai H, Fukui D, Futamata N, Mawatari K, Oba T, Nagata T, Kyougoku S, Koga M, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 147 Pages: 258-264
• [Journal Article] Reduction and activation of circulating dendritic cells in patients with decompensated heart failure (2011)
  • Author(s): Yusuke Sugi
  • Journal Title: International Journal of Cardiology Volume: 147 Issue: 2 Pages: 258-264
  • DOI: 10.1016/j.ijcard.2009.09.524
  • Peer Reviewed
• [Presentation] The role of dendritic cells in the pathogenesis of heart failure (2010)
  • Author(s): Yasukawa H, Sugi Y, Ohshima H, Imaizumi T
  • Organizer: The Molecular mechanism of myocarditis and heart failureKyoto(The XX World Congress of the ISHR(International Society for Heart Research)
• [Presentation] Cardiac-specific deletion of SOCS3 prevented myocardial apoptosis after acute myocardial infarction via inhibiting mitochondrial damage (2010)
  • Author(s): Oba T, Yasukawa H, Sasaki K, Futamata N, Mawatari K, Nagata T, Kyogoku S, Ohshima H, Fukui D, Sugi Y, Imaizumi T
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都