| Project/Area Number |
17590721
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
HORIBA Mitsuru Res.Inst.of Environ.Med., Assistant Professor, 環境医学研究所, 助手 (40345913)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Itsuo Res.Inst.of Environ.Med., Professor, 環境医学研究所, 教授 (30124720)
KADAMA Itsuo School of Medicine.Dept.of Biochemistry, Professor, 大学院医学系研究科, 教授 (80204519)
YASUI Kenji Res.Inst.of Environ.Med., Professor, 環境医学研究所, 教授 (70283471)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | midkine / apoptosis / remodeling / ミッドカイン(MK) / 虚血性心筋障害 |
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| Research Abstract |
Midkine (MK) is a heparin-binding growth factor involved in diverse biological phenomena such as tissue repair and neural survival. We have demonstrated recently that MK ameliorates myocardial injury in mice suffering from acute ischemia though the anti-apoptotic action. In this study we investigated the long-term effects of MK on the left ventricular (LV) remodeling after myocardial infarction (MI). The MK-deficient (MKKO) mice showed a higher mortality, a greater LV dysfunction and fibrosis, and less angiogenesis in the peri-infarct zone compared with wild-type (WT) mice. Supplemental application of MK (8 μg/day, i.p., 14 days) to MKKO reversed the higher mortality, greater LV remodeling and less angiogenesis. Exogenous MK application (8 μg/day, i.p., 28 days) to WT subjected to MI improved the survival, and ameliorated LV dysfunction and fibrosis. These changes were associated with an enhancement of PI3K expression and Akt phosphorylation. In-vitro experiments using human umbilical vein endothelial cells (HUVEC) confirmed the potent angiogenetic action of MK via the PI3K/Akt pathway. MK application could be a new therapeutic strategy for the treatment of ischemic heart failure.
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