| Project/Area Number |
22390068
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
FAN Jianglin 山梨大学, 大学院・医学工学総合研究部, 教授 (60272192)
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| Co-Investigator(Kenkyū-buntansha) |
KITAJIMA Shuji 佐賀大学, 総合分子実験センター, 准教授 (70284643)
KOIKE Tomonari 神戸大学, 医学(系)研究科(研究院), 助教 (40432158)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIBATA Nobumitsu 山梨大学, 医学工学総合研究部, 助教 (40452130)
SHIOMI Masashi 神戸大学, 医学(系)研究科(研究院), 准教授 (50226106)
TEZUKA Hideo 山梨大学, 総合分析実験センター, 准教授 (70155456)
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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 |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2012: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2010: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
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| Keywords | 高脂血症 / 動脈硬化 / 遺伝子改変ウサギ / HDL / アンチセンス / 内皮リパーゼ / ウサギ / EL / 遺伝子改変 / リパーゼ / ウサギモデル |
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| Research Abstract |
Existing evidence suggests that endothelial lipase (EL) plays an important role inhigh-density-lipoprotein (HDL) metabolism. First, we cloned the rEL cDNA and gene ofrabbits. Using Northern blotting, real-time RT-PCR, Western blotting, and in situhybridization, we revealed that rEL mRNA was highly expressed in the cholesterolsynthesis-related organs including the liver, testis, and adrenal along with itsexpression in the lung, kidney, bone marrow, and small intestine. The plasma HDL levelsin WHHL rabbits were inversely associated with high levels of plasma rEL proteins andhepatic expression of rEL mRNA. Injection of rEL-specific antisense oligonucleotides intorabbits resulted in an elevation of plasma large-sized HDLs. Furthermore, we demonstratedthat the rEL mRNA was expressed by both endothelial cells and macrophages in the lesionsof aortic atherosclerosis of WHHL rabbits. rEL is expressed in multiple tissues and mayhave many physiological and pathophysiological functions such as in the regulation ofcholesterol metabolism and atherosclerosis. Our results suggest that EL is an importantregulator of plasma HDL levels in rabbits. In addition, we generated two transgenicrabbits expressing different levels of human EL in the liver
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