A Macrophage Sterol-Responsive Network Linked to Atherogenesis

被引：66

作者：

Becker, Lev ^{[1
]}

Gharib, Sina A. ^{[1
]}

Irwin, Angela D. ^{[1
]}

Wijsman, Ellen ^{[1
,2
]}

Vaisar, Tomas ^{[1
]}

Oram, John F. ^{[1
]}

Heinecke, Jay W. ^{[1
]}

机构：

[1] Univ Washington, Dept Med, Seattle, WA 98195 USA

[2] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

来源：

CELL METABOLISM | 2010年 / 11卷 / 02期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

FOAM-CELL-FORMATION; STATISTICAL-MODEL; DEFICIENT MICE; ATHEROSCLEROSIS; INFLAMMATION; INHIBITION; EXPRESSION; PROTEINS; DATABASE; INDEX;

D O I：

10.1016/j.cmet.2010.01.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cholesteryl ester accumulation by macrophages is a critical early event in atherogenesis. To test the hypothesis that sterol loading promotes foam cell formation and vascular disease by perturbing a network of interacting proteins, we used a global approach to identify proteins that are differentially expressed when macrophages are loaded with cholesterol in vivo. Our analysis revealed a sterol-responsive network that is highly enriched in proteins with known physical interactions, established roles in vesicular transport, and demonstrated atherosclerotic phenotypes in mice. Pharmacologic intervention with a statin or rosiglitazone and use of mice deficient in LDL receptor or apolipoprotein E implicated the network in atherosclerosis. Biochemical fractionation revealed that most of the sterol-responsive proteins resided in microvesicles, providing a physical basis for the network's functional and biochemical properties. These observations identify a highly integrated network of proteins whose expression is influenced by environmental, genetic, and pharmacological factors implicated in atherogenesis.

引用

页码：125 / 135

页数：11

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