Lack of macrophage fatty-acid–binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis

被引：573

作者：

Liza Makowski ^{[1
]}

Jeffrey B. Boord ^{[2
]}

Kazuhisa Maeda ^{[1
]}

Vladimir R. Babaev ^{[2
]}

K. Teoman Uysal ^{[1
]}

Maureen A. Morgan ^{[5
]}

Rex A. Parker ^{[5
]}

Jill Suttles ^{[6
]}

Sergio Fazio ^{[2
]}

Gökhan S. Hotamisligil ^{[3
]}

MacRae F. Linton ^{[1
]}

机构：

[1] Harvard School of Public Health,Division of Biological Sciences and Department of Nutrition

[2] Vanderbilt University Medical Center,Department of Medicine

[3] Vanderbilt University Medical Center,Department of Pathology

[4] Vanderbilt University Medical Center,Department of Pharmacology

[5] Bristol-Myers Squibb PRI,Department of Metabolic Research

[6] University of Louisville School of Medicine,Department of Microbiology and Immunology

来源：

Nature Medicine | 2001年 / 7卷 / 6期

关键词：

D O I：

10.1038/89076

中图分类号：

学科分类号：

摘要：

The adipocyte fatty-acid–binding protein, aP2, has an important role in regulating systemic insulin resistance and lipid metabolism. Here we demonstrate that aP2 is also expressed in macrophages, has a significant role in their biological responses and contributes to the development of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice also deficient for aP2 showed protection from atherosclerosis in the absence of significant differences in serum lipids or insulin sensitivity. aP2-deficient macrophages showed alterations in inflammatory cytokine production and a reduced ability to accumulate cholesterol esters when exposed to modified lipoproteins. Apoe−/− mice with Ap2+/+ adipocytes and Ap2−/− macrophages generated by bone-marrow transplantation showed a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macrophage aP2 in atherogenesis. Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrome and could be a new therapeutic target for the prevention of atherosclerosis.

引用

页码：699 / 705

页数：6