| Project/Area Number |
24390203
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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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)
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| 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)
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| Research Collaborator |
NAKANO Astushi
IHARA Madoka
MIN Kyung-Duk
ITO Shin
SHINDO Kazuhiro
IMAZU Miki
TAKAHASHI Ayako
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2012: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
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| Keywords | アデノシン / 心不全 / トランスレーショナル研究 |
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| 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.
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