Development of new heart failure treatment using DPP-4 inhibitors-The role of adenosine

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390203
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: KITAKAZE Masafumi 独立行政法人国立循環器病研究センター, 研究開発基盤センター, 部長 (20294069)
• Co-Investigator(Kenkyū-buntansha): ASANUMA Hiroshi 京都府立医科大学, 医学研究科, 特任准教授 (20416217) ; ASAKURA Masanori 国立循環器病研究センター, 研究開発基盤センター, 室長 (80443505) ; YAMAZAKI Satoru 国立循環器病研究センター, 研究所, 室長 (70348796)
• Research Collaborator: NAKANO Astushi ; IHARA Madoka ; MIN Kyung-Duk ; ITO Shin ; SHINDO Kazuhiro ; IMAZU Miki ; TAKAHASHI Ayako
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: アデノシン / 心不全 / トランスレーショナル研究

Outline of Final Research Achievements

It has been reported that GLP-1 and DPP-4 inhibitors improves the pathophysiology of heart failure (HF). On the other hand, adenosine is a well-established cardioprotective molecule. Interestingly, several reports have indicated that DPP-4 forms a complex with adenosine deaminase (ADA) in immune cells and that ADA regulates DPP-4-mediated intracellular signaling. Because circulating adenosine is eliminated by ADA activity, ADA inhibition by DPP-4 inhibitors may mediated cardioprotection via an adenosine-dependent mechanisms. The present study elucidated the cardioprotective mechanism of DPP-4 inhibitor in various models of HF. The increase in GLP-1 level induce by DPP-4 inhibitor reduces myocardial damage via GLP-1 receptor-mediated activation of the adenosine A1 receptor-PKC α-cAMP response element binding protein (CREB) signaling cascade in ischemia-reperfusion model. These findings support the therapeutic potential of this interaction between GLP-1 and adenosine for HF.

Free Research Field

循環器内科学