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Circ Res. 2014 Oct 10;115(9):770-780. doi: 10.1161/CIRCRESAHA.115.304666. Epub 2014 Sep 3.

CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure.

Author information

1
Division of Cardiovascular Medicine, University of Maryland Baltimore, Maryland, USA.
2
Department of Pharmacology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
3
The Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA.
4
Center for Integrative Toxicology and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA.
5
College of Public Health, The Ohio State University, Columbus, Ohio, USA.
#
Contributed equally

Abstract

RATIONALE:

Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis are not fully understood.

OBJECTIVE:

To investigate the mechanisms by which particulate matter <2.5 μm (PM2.5) induces progression of atherosclerosis.

METHODS AND RESULTS:

Atherosclerosis-prone ApoE(-/-) or LDLR(-/-) mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma intermediate density lipoprotein/low-density lipoprotein fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis.

CONCLUSIONS:

Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids, such as 7-KCh, in air pollution-induced atherosclerosis progression.

KEYWORDS:

7-ketocholesterol; air pollution; atherosclerosis; foam cells; macrophages; particulate matter

PMID:
25186795
PMCID:
PMC4275116
DOI:
10.1161/CIRCRESAHA.115.304666
[Indexed for MEDLINE]
Free PMC Article

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