| Project/Area Number |
21790709
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
IWATA Hiroshi The University of Tokyo, 医学部附属病院, 助教 (00451807)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 動脈硬化 / 細胞起源 / 骨髄由来細胞 / 平滑筋細胞 / 分子メカニズム |
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| Research Abstract |
Background-It has been proposed that bone marrow-derived cells infiltrate the neointima, where they differentiate into smooth muscle (SM) cells ; however, technical limitations have hindered clear identification of the lineages of bone marrow-derived "SM cell-like" cells.
Methods and Results-Using a specific antibody against the definitive SM cell lineage marker SM myosin heavy chain (SM-MHC) and mouse lines in which reporter genes were driven by regulatory programs for either SM-MHC or SMα-actin, we demonstrated that although some bone marrow-derived cells express SMα-actin in the wire injury-induced neointima, those cells did not express SM-MHC, even 30 weeks after injury. Likewise, no SM-MHC+ bone marrow-derived cells were found in vascular lesions in apolipoprotein E-/-mice or in a heart transplantation vasculopathy model. Instead, the majority of bone marrow-derived SMα-actin+ cells were also CD115+CD11b+F4/80+Ly-6C+, which is the surface phenotype of inflammatory monocytes. Moreover, adoptively transferred CD11b+Ly-6C+ bone marrow cells expressed SMα-actin in the injured artery. Expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow-derived SM α-actin+ cells than in other regions.
Conclusions-It appears that bone marrow-derived SMα-actin+ cells are of monocyte/macrophage lineage and are involved in vascular remodeling. It is very unlikely that these cells acquire the definitive SM cell lineage.
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