Format

Send to

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

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

Author information

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

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.

PMID:
11385507
PMCID:
PMC4027052
DOI:
10.1038/89076
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center