MACROPHAGE EXPRESSION OF APOAI AND ATHEROSCLEROSIS
APOAI 和动脉粥样硬化的巨噬细胞表达
基本信息
- 批准号:6760012
- 负责人:
- 金额:$ 33.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-07-01 至 2005-06-30
- 项目状态:已结题
- 来源:
- 关键词:apolipoprotein Eapolipoproteinsatherosclerosisblood lipoprotein metabolismbone marrow transplantationcellular pathologycholesterolcomplementary DNAdisease /disorder modelgene expressiongene targetinggene therapygenetically modified animalshigh density lipoproteinslaboratory mouseleukocyte activation /transformationlipid metabolismlipid transportlipoprotein lipaselow density lipoprotein receptormacrophagemodel design /developmentmolecular pathologytissue /cell culturevascular endothelium
项目摘要
DESCRIPTION: (adapted from abstract) Recruitment of monocyte/macrophages into
the subendothelial space is a mandatory step in the transition between vascular
health and atherosclerotic lesion formation. Accumulation of lipids within the
cytoplasm induces the transformation of macrophages into metabolically inert
foam cells. Efflux of cholesterol from the macrophages cannot only delay foam
cell formation but also activates reverse cholesterol transport. Apolipoprotein
(apo) AI is one of the major physiologic determinants of cholesterol efflux
from cells, but is not expressed by tissue macrophages. In previous studies,
the applicant has shown that macrophage production of apoE (another acceptor of
intracellular cholesterol) directly influences lesion formation in inbred
C57BL/6 mice. Dr. Fazio hypothesizes that, if given the ability to produce
apoAI, macrophages would be more efficient in getting rid of cholesterol and in
activating HDL metabolism. To this end, his group has produced several lines of
transgenic mice expressing the human apoAI under the control of a
macrophage-specific promoter. In addition, they have developed a viable method
for transduction of bone marrow with a retrovirus carrying the apoAI cDNA, and
shown that transplantation of transduced marrow into irradiated mice will
result in expression of apoAI from macrophages. The objectives of this research
program are: i) To create and characterize transgenic mice with the ability to
produce apoAI from the macrophage; ii) To evaluate the effect of macrophage
apoAI expression on lipids and atherosclerosis in C57BL/6 mice and in mice
lacking either the apoAI or the apoE gene; iii) To evaluate the effect of
macrophage apoAI in ACAT-1-/- mice, a model of free cholesterol toxicity and
inappropriate efflux; iv) To evaluate the feasibility of marrow transduction as
a method for ex vivo delivery of apoAI to the macrophage. These studies can be
expected to delineate the biology of foam cell formation and the importance of
cholesterol efflux in atherogenesis. Moreover, these studies may lay the basis
for a gene therapy approach to atherosclerosis.
描述:(改编自摘要)募集单核细胞/巨噬细胞进入
项目成果
期刊论文数量(0)
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SERGIO FAZIO其他文献
SERGIO FAZIO的其他文献
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{{ truncateString('SERGIO FAZIO', 18)}}的其他基金
Functional and structural correlates of PCSK9 association with lipoproteins
PCSK9 与脂蛋白关联的功能和结构相关性
- 批准号:
9335438 - 财政年份:2016
- 资助金额:
$ 33.98万 - 项目类别:
Functional and structural correlates of PCSK9 association with lipoproteins
PCSK9 与脂蛋白关联的功能和结构相关性
- 批准号:
9155814 - 财政年份:2016
- 资助金额:
$ 33.98万 - 项目类别:
PCSK9, Lipoprotein receptors, and Atherosclerosis
PCSK9、脂蛋白受体和动脉粥样硬化
- 批准号:
8248701 - 财政年份:2011
- 资助金额:
$ 33.98万 - 项目类别:
PCSK9, Lipoprotein receptors, and Atherosclerosis
PCSK9、脂蛋白受体和动脉粥样硬化
- 批准号:
8606492 - 财政年份:2011
- 资助金额:
$ 33.98万 - 项目类别:
PCSK9, Lipoprotein receptors, and Atherosclerosis
PCSK9、脂蛋白受体和动脉粥样硬化
- 批准号:
8436303 - 财政年份:2011
- 资助金额:
$ 33.98万 - 项目类别:
PCSK9, Lipoprotein receptors, and Atherosclerosis
PCSK9、脂蛋白受体和动脉粥样硬化
- 批准号:
8131556 - 财政年份:2011
- 资助金额:
$ 33.98万 - 项目类别:
MACROPHAGE EXPRESSION OF APOAI AND ATHEROSCLEROSIS
APOAI 和动脉粥样硬化的巨噬细胞表达
- 批准号:
6390892 - 财政年份:2000
- 资助金额:
$ 33.98万 - 项目类别:
MACROPHAGE EXPRESSION OF APOAI AND ATHEROSCLEROSIS
APOAI 和动脉粥样硬化的巨噬细胞表达
- 批准号:
6191927 - 财政年份:2000
- 资助金额:
$ 33.98万 - 项目类别:
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