| Project/Area Number |
18K15060
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Akita University (2019)
Tokyo Medical and Dental University (2018) |
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Principal Investigator |
An Jianbo 秋田大学, 医学系研究科, 助教 (40723771)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 動脈硬化症 / MKL1 / マクロファージ / 細胞増殖 / MRTF-A / 動脈硬化 / 脂肪萎縮症 |
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| Outline of Final Research Achievements |
It has been reported that promoter polymorphism of MKL1 is associated with coronary atherosclerosis. However, the contribution of MKL1 to the development of atherosclerosis remains unclear. Macrophages are known to be important mediators of atherosclerosis. In this study, it was found that MKL1 was highly expressed in lesional macrophages in human carotid atherosclerotic plaque. To investigate the role of macrophagic MKL1 in the pathogenesis of atherosclerosis, I generated ApoE null MKL1 transgenic mice (ApoE-KO/MKL1-TgM), in which human MKL1 was specifically overexpressed in monocytes/macrophages. ApoE-KO/MKL1-TgM aggravated atherosclerosis and accumulated prominent lesional macrophages in the aortic sinus. It was also found that MKL1 promoted proliferation of macrophages and mitigated apoptosis both in vitro and in vivo due to downregulation of the expression of CDKI.
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| Academic Significance and Societal Importance of the Research Achievements |
冠動脈硬化症の成因については、生活習慣の蓄積と同時に、遺伝的背景が発症や進展を左右することが知られており、従って、ゲノム多様性の観点から、冠動脈硬化症の形成機構を分子レベルで解明し、その知見を予防または治療に繋ぐ研究成果を提供することが、社会的にも要請されている。先行研究において、網羅的ゲノム解析から新たな冠動脈疾患関連遺伝子座としてのMKL1遺伝子多型の同定し、本研究課題において、MKL1による動脈硬化症の分子機構を明らかにすることは、とりわけ世界的にも例のない高齢化社会を迎えているわが国において、健康長寿社会を実現するために必要な研究成果である。
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