title: Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice.
abstract: Exposure to ambient particulate matter (PM) is a risk factor for cardiovascular diseases. The redox-active ultrafine particles (UFPs) promote vascular oxidative stress and inflammatory responses. We hypothesized that UFPs modulated lipid metabolism and anti-oxidant capacity of high density lipoprotein (HDL) with an implication in atherosclerotic lesion size. Fat-fed low density lipoprotein receptor-null (LDLR⁻/⁻ mice were exposed to filtered air (FA) or UFPs for 10 weeks with or without administering an apolipoprotein A-I mimetic peptide made of D-amino acids, D-4F. LDLR⁻/⁻ mice exposed to UFPs developed a reduced plasma HDL level (P < 0.01), paraoxonase activity (P < 0.01), and HDL anti-oxidant capacity (P < 0.05); but increased LDL oxidation, free oxidized fatty acids, triglycerides, serum amyloid A (P < 0.05), and tumor necrosis factor α (P < 0.05), accompanied by a 62% increase in the atherosclerotic lesion ratio of the en face aortic staining and a 220% increase in the cross-sectional lesion area of the aortic sinus (P < 0.001). D-4F administration significantly attenuated these changes. UFP exposure promoted pro-atherogenic lipid metabolism and reduced HDL anti-oxidant capacity in fat-fed LDLR⁻/⁻ mice, associated with a greater atherosclerotic lesion size compared with FA-exposed animals. D-4F attenuated UFP-mediated pro-atherogenic effects, suggesting the role of lipid oxidation underlying UFP-mediated atherosclerosis.
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA; Division of Cardiology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA; and.
authors.forename: Rongsong
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA; and.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.affiliation: Department of Civil Engineering and Environmental Science, and University of Southern California, Los Angeles, CA.
authors.forename: Payam
authors.initials: P
authors.lastname: Pakbin
authors.affiliation: School of Energy and Environment, City University of Hong Kong, Hong Kong.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA; and.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Navab
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA; and.
authors.forename: Greg
authors.initials: G
authors.lastname: Hough
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA.
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA; and.
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Araujo
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA; and.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
authors.affiliation: Department of Civil Engineering and Environmental Science, and University of Southern California, Los Angeles, CA.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA; Division of Cardiology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA; and. Electronic address: hsiai@usc.edu.
authors.forename: Tzung
authors.initials: T
authors.lastname: Hsiai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000494:pharmacology; D050197:Atherosclerosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction / Q000187:drug effects; D052638:Particulate Matter / Q000009:adverse effects* / Q000494:pharmacology; D057786:Peptidomimetics / Q000494:pharmacology; D011973:Receptors, LDL
chemical_list: D000975:Antioxidants; D016632:Apolipoprotein A-I; C465468:D-4F peptide; D004041:Dietary Fats; D008075:Lipoproteins, HDL; D052638:Particulate Matter; D057786:Peptidomimetics; D011973:Receptors, LDL
keywords: D-4F; atherosclerosis; high density lipoprotein; low density lipoprotein receptor-null
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