Lack of Macrophage Fatty-acid-binding Protein AP2 Protects Mice Deficient in Apolipoprotein E Against Atherosclerosis

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2001 Jun 1

PMID 11385507

Citations 304

Authors

Liza Makowski

Jeffrey B Boord

Kazuhisa Maeda

Vladimir R Babaev

K Teoman Uysal

Maureen A Morgan

Rex A Parker

Jill Suttles

Sergio Fazio

Gokhan S Hotamisligil

MacRae F Linton

Affiliations

Soon will be listed here.

Abstract

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.

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