| Project/Area Number |
22590783
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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 | Kobe University |
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Principal Investigator |
KAWAI Hiroya 神戸大学, 大学院・医学研究科, 教授 (20346266)
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| Co-Investigator(Kenkyū-buntansha) |
TOH Ryuji 神戸大学, 医学研究科, 准教授 (50379418)
石田 達郎 神戸大学, 医学部附属病院, 准教授 (00379413)
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| Co-Investigator(Renkei-kenkyūsha) |
ISHIDA Tatsuro 神戸大学, 医学部附属病院, 准教授 (00379413)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 心不全 / 高比重リポ蛋白 / 炎症 / 脂質代謝 / 血管内皮 / リパーゼ / 脂肪酸 / HDL / エネルギー / 心筋 / リポ蛋白 / 循環器 / 心肥大 |
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| Research Abstract |
Under normal conditions, the heart utilizes nearly 70% of itsenergy through the oxidation of fatty acids (FA). FA are supplied to the heart from the hydrolysis of triglyceride-rich lipoproteins by triglyceride lipase members. Lipoprotein lipase(LPL) has been considered as the only enzyme capable of this function. Endothelial lipase (EL) exhibits primarily phospholipase activity against high-density lipoproteins, but to a lesser extent, triglyceridelipase activity. In this study, we evaluated the role of cardiac EL under conditions of increased energy needs. Pressure overload-induced cardiac hypertrophy was generated in C57Bl/6 mice by ascending aortic constriction, and EL expression in the hypertrophied hearts was evaluated. Cardiac EL expression was elevated in the early stage of cardiac hypertrophy. Complementary cell culture experiments using rat neonatal cardiomyocytes revealed that inflammatory cytokines and lipopolysaccharides increased EL expression in cardiomyocytes, while LPL was decreased by the inflammatory stimuli. In addition, the inflammatory stimuli-induced EL expression was inversely correlated with the expression of carnitine palmitoyltransferase Ib, which is a key enzyme involved in the regulation of FA oxidation and utilization. Furthermore, cardiac EL expression was associated with its function. EL may be an alternative pathway to supply FA to the heart and regulate cardiac function. This function was likely relevant particularly under inflammatory conditions where LPL is downregulated.
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