| Project/Area Number |
21590947
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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 | The University of Tokyo |
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Principal Investigator |
IIJIMA Katsuya 東京大学, 高齢社会総合研究機構, 准教授 (00334384)
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| Co-Investigator(Kenkyū-buntansha) |
ETO Masato 東京大学, 医学部附属病院, 特任准教授 (80282630)
OTA Hidetaka 東京大学, 医学部附属病院, 助教 (20431869)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 血管石灰化 / 細胞老化 / 長寿遺伝子Sirtuin / 動脈硬化 / 長寿遺伝子 |
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| Research Abstract |
Vascular aging manifest several features, namely atherosis, sclerosis and calcified change. Vascular calcification makes the management of hemodynamics more difficult in the elderly, because the stiffened vasculatures with ectopic calcification contribute to excessive blood pressure variability, isolated systolic hypertension with increased arterial wave reflectance, and subsequent ischemic cerebro-/cardio-vascular(CV) events. Vascular calcification has been previously shown to result from passive precipitation of calcium with aging and osteoporosis. However, accumulating recent evidences have shown it to be attributable to an active' cell-mediated process' resembling osteogenesis in bone rather than passive mineral precipitation in vascular smooth muscle cells(SMC). Cellular senescence has been recently shown to be linked to atherosclerogenesis ; however, few reports have addressed whether cellular senescence is associated with SMC calcification. Our new findings show that the senescent phenotypic change is associated with osteoblastic trans-differentiation in SMC and mammalian sirtuin SIRT1, which is well known as a longevity gene, can exert a protective effect on the cellular senescence-related vascular calcification under hyperphosphatemia. In addition, the activation of Runx2, a potent osteogenic transcriptional factor, in SMC is regulated by SIRT1-p21 axis. The identification of therapeutic targets which can slow down the progression or even reverse the senescent phenotypic change in SMC could be an important step forward in the treatment of vascular calcification.
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