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

Liza Makowski; Jeffrey B Boord; Kazuhisa Maeda; Vladimir R Babaev; K Teoman Uysal; Maureen A Morgan; Rex A Parker; Jill Suttles; Sergio Fazio; Gökhan S Hotamisligil; MacRae F Linton

doi:10.1038/89076

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

Nat Med. 2001 Jun;7(6):699-705. doi: 10.1038/89076.

Authors

Affiliations

¹ Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
² Departments of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Bristol-Myers Squibb PRI, Department of Metabolic Research, Princeton, New Jersey, USA.
⁴ Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
⁵ Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁶ Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

^# Contributed equally.

PMID: 11385507
PMCID: PMC4027052
DOI: 10.1038/89076

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adipocytes / physiology*
Animals
Aorta / cytology
Apolipoproteins E / metabolism*
Arteriosclerosis / etiology
Arteriosclerosis / physiopathology*
Arteriosclerosis / prevention & control
Bone Marrow Transplantation
Carrier Proteins / metabolism*
Cell Line
Cholesterol Esters / metabolism
Diet
Fatty Acid-Binding Protein 7
Fatty Acid-Binding Proteins
Female
Foam Cells / physiology
Glucose / metabolism
Humans
Insulin / metabolism
Interleukin-1 / genetics
Interleukin-1 / metabolism
Interleukin-6 / genetics
Interleukin-6 / metabolism
Lipids / blood
Macrophages / physiology*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasm Proteins*
Nerve Tissue Proteins*
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism
Tumor Suppressor Proteins*

Substances

Apolipoproteins E
Carrier Proteins
Cholesterol Esters
FABP7 protein, human
Fabp5 protein, mouse
Fabp7 protein, mouse
Fatty Acid-Binding Protein 7
Fatty Acid-Binding Proteins
Insulin
Interleukin-1
Interleukin-6
Lipids
Neoplasm Proteins
Nerve Tissue Proteins
Tumor Necrosis Factor-alpha
Tumor Suppressor Proteins
Glucose

Abstract

Publication types

MeSH terms

Substances

Grants and funding