title: CD36-dependent 7-ketocholesterol accumulation in macrophages mediates progression of atherosclerosis in response to chronic air pollution exposure.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland Baltimore, Maryland, USA.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Rao
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland Baltimore, Maryland, USA.
authors.forename: Jixin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland Baltimore, Maryland, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Maiseyeu
authors.affiliation: Department of Pharmacology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Bhavani
authors.initials: B
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Pharmacology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Villamena
authors.affiliation: The Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA.
authors.forename: Lung-Chi
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Center for Integrative Toxicology and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Harkema
authors.affiliation: Department of Pharmacology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.|College of Public Health, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland Baltimore, Maryland, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000209:etiology* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D001692:Biological Transport; D018955:CD36 Antigens / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005487:Foam Cells / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D019570:Inhalation Exposure; D007653:Ketocholesterols / Q000097:blood*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010316:Particle Size; D052638:Particulate Matter; D058226:Plaque, Atherosclerotic; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D007653:Ketocholesterols; D052638:Particulate Matter; D011973:Receptors, LDL; C003001:7-ketocholesterol
keywords: 7-ketocholesterol; air pollution; atherosclerosis; foam cells; macrophages; particulate matter