2019 Fiscal Year Final Research Report
Function of apoE in lipoprotein metabolism and atherosclerosis: insight from apoE-deficient rabbit model
Project/Area Number |
17K08783
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | University of Yamanashi |
Principal Investigator |
NIIMI Manabu 山梨大学, 大学院総合研究部, 助教 (80644898)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 脂質異常症 / リポタンパク代謝 / アポE / ウサギ / 遺伝子欠損 |
Outline of Final Research Achievements |
Apolipoprotein E (apoE) is a 34 kDa glycoprotein and its role on lipid metabolism is a ligand for lipoprotein receptor on the liver. We created apoE-deficient model using rabbits, which have more similar lipoprotein metabolism to humans than mice. To investigate the role of apoE in lipoprotein metabolism and atherosclerosis, we analyzed plasma lipids, lipoproteins and susceptibility to a diet-induced atherosclerosis of apoE-deficient rabbits. ApoE-deficent rabbits showed higher plasma total cholesterol and triglycerides levels than those of wild-type rabbits on a high cholesterol-diet. This increase was due to an elevated plasma βVLDL, and the βVLDL showed enriched apoB-48. Our studies revealed that deficiency of apoE in rabbits promotes aortic atherosclerosis.
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Free Research Field |
病態医化学
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Academic Significance and Societal Importance of the Research Achievements |
脂質異常症は動脈硬化を引き起こす原因の一つで、心筋梗塞などの心血管疾患における重要な危険因子である。脂質異常症は遺伝素因、生活習慣などさまざまな原因で発症する。アポリポ蛋白E(アポE)もその原因の一つで、アポEに変異や欠損が生じると血中リポ蛋白の肝臓での受容体結合能が低下し、Ⅲ型高脂血症を引き起こす。これまでにアポE欠損マウスを用いた研究が盛んに行われてきた。本研究ではマウスに比べてヒトにより近いリポ蛋白代謝系を持つウサギを用いてアポEのリポ蛋白代謝及び動脈硬化形成・進展における役割を明らかにした。
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