title: Diesel exhaust induces systemic lipid peroxidation and development of dysfunctional pro-oxidant and pro-inflammatory high-density lipoprotein.
abstract: OBJECTIVE
  To evaluate whether exposure to air pollutants induces oxidative modifications of plasma lipoproteins, resulting in alteration of the protective capacities of high-density lipoproteins (HDLs).
  
  
  RESULTS
  We exposed apolipoprotein E-deficient mice to diesel exhaust (DE) at ≈ 250 µg/m(3) for 2 weeks, filtered air (FA) for 2 weeks, or DE for 2 weeks, followed by FA for 1 week (DE+FA). DE led to enhanced lipid peroxidation in the brochoalveolar lavage fluid that was accompanied by effects on HDL functionality. HDL antioxidant capacity was assessed by an assay that evaluated the ability of HDL to inhibit low-density lipoprotein oxidation estimated by 2',7'-dichlorofluorescein fluorescence. HDL from DE-exposed mice exhibited 23,053 ± 2844 relative fluorescence units, higher than FA-exposed mice (10,282 ± 1135 relative fluorescence units, P<0.001) but similar to the HDL from DE+FA-exposed mice (22,448 ± 3115 relative fluorescence units). DE effects on HDL antioxidant capacity were negatively correlated with paraoxonase enzymatic activity, but positively correlated with levels of plasma 8-isoprostanes, 12-hydroxyeicosatetraenoic acid, 13-hydroxyoctadecadienoic acid, liver malondialdehyde, and accompanied by perturbed HDL anti-inflammatory capacity and activation of the 5-lipoxygenase pathway in the liver.
  
  
  CONCLUSIONS
  DE emissions induced systemic pro-oxidant effects that led to the development of dysfunctional HDL. This may be one of the mechanisms by which air pollution contributes to enhanced atherosclerosis.
authors.affiliation: Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Fen
authors.initials: F
authors.lastname: Yin
authors.forename: Akeem
authors.initials: A
authors.lastname: Lawal
authors.forename: Jerry
authors.initials: J
authors.lastname: Ricks
authors.forename: Julie R
authors.initials: JR
authors.lastname: Fox
authors.forename: Tim
authors.initials: T
authors.lastname: Larson
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rosenfeld
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Araujo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000378:metabolism; D004195:Disease Models, Animal; D019570:Inhalation Exposure / Q000009:adverse effects*; D015227:Lipid Peroxidation; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values; D015398:Signal Transduction; D001335:Vehicle Emissions
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D008315:Malondialdehyde; D001094:Arachidonate 5-Lipoxygenase; D043303:Aryldialkylphosphatase
keywords: air pollution; diesel exhaust; dysfunctional high-density lipoproteins; oxidative stress