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ApoE in Cholesterol and Triglyceride Homeostasis

ApoE in Cholesterol and Triglyceride Homeostasis
ApoE 在胆固醇和甘油三酯稳态中的作用
批准号:
6655556
负责人:
VASSILIS I ZANNIS
金额:
$28.53万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-09-01 至 2005-08-31

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中文摘要
翻译
描述(由申请人提供):载脂蛋白E (apoE)是一个重要的
英文摘要
DESCRIPTION (provided by applicant): Apolipoprotein E (apoE) is an important protein of the cholesterol transport system. ApoE is responsible for the clearance of lipoprotein remnants from the circulation via lipoprotein receptors, contributes to cholesterol homeostasis, and protects from atherosclerosis. ApoE has also been shown to have other functions which contribute to cholesterol and triglyceride homeostasis, including VLDL triglyceride secretion and VLDL lipolysis, two processes which may affect plasma triglyceride levels. It is our hypothesis, which is supported by preliminary data, that the carboxy terminal domain of apoE is responsible for the hypertriglyceridemia which is induced by overexpression of apoE. We also hypothesize that overexpression of carboxy terminal apoE variants may protect from atherosclerosis. Our specific aims are: 1) To use adenovirus-mediated gene transfer as well as transgenic mice to elucidate the role of apoE in triglyceride homeostasis and establish the mechanism of apoE-induced hypertriglyceridemia in vivo. 2) To use adenovirus-mediated gene transfer of different apoE forms (in appropriate receptor-deficient mouse models) to elucidate the role of apoE receptors in cholesterol clearance in vivo and in vitro. The mouse models that will be utilized for gene transfer are apoE-/-, LDLR-/-, liver-specific LRP-/- mice as well as crosses among these The gene transfer and receptor binding studies will define the ligand speciflcities for different receptors. 3) To express long-term apoE forms that do not induce hypertriglyceridemia using adenoassociated viral vectors (AAV-apoE) and transgenic mice in order to correct the hypercholesterolemic and atherogenic profile of apoE-deficient mice. This specific aim will explore the ability of selected truncated and mutant forms of apoE that do not induce hypertriglyceridemia to protect from atherosclerosis. We expect that apoE forms that can clear cholesterol and triglycerides and protect from atherosclerosis may provide new therapeutic tools in the near future for the correction of remnant removal disorders.
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INTRACELLULAR MODIFICATIONS OF HUMAN APOLIPOPROTEIN E
  • 批准号:
    7723008
  • 项目类别:
  • 资助金额:
    $0.13万
  • 财政年份:
    2008
  • 负责人:
    VASSILIS I ZANNIS
  • 依托单位:
INTRACELLULAR MODIFICATIONS OF HUMAN APOLIPOPROTEIN E
  • 批准号:
    7602002
  • 项目类别:
  • 资助金额:
    $0.22万
  • 财政年份:
    2007
  • 负责人:
    VASSILIS I ZANNIS
  • 依托单位:
INTRACELLULAR MODIFICATIONS OF HUMAN APOLIPOPROTEIN E
  • 批准号:
    7369267
  • 项目类别:
  • 资助金额:
    $0.69万
  • 财政年份:
    2006
  • 负责人:
    VASSILIS I ZANNIS
  • 依托单位:
INTRACELLULAR MODIFICATIONS OF HUMAN APOLIPOPROTEIN E
  • 批准号:
    7182222
  • 项目类别:
  • 资助金额:
    $0.69万
  • 财政年份:
    2005
  • 负责人:
    VASSILIS I ZANNIS
  • 依托单位:
海外基金