Abstract 386: Air Pollutants Induce Dysfunctional Prooxidant HDL and Activate 5-lipoxygenase in the Liver
Background Exposure to ambient particulate matter is associated with increased cardiovascular ischemic events and enhanced atherosclerosis.
Objective To test our hypothesis that air pollutants may induce oxidative modifications of plasma lipoproteins resulting in alteration of the anti-oxidant and anti-inflammatory properties of high-density lipoproteins (HDL).
Methods and Results We exposed ApoE-/- male mice (C57BL/6 background) to diesel exhaust (DE) emissions at 250 μg PM2.5/m3 for two weeks, filtered air (FA) for two weeks or DE for two weeks, followed by FA for one week (DE+FA). HDL anti-oxidant capacity was assessed by a DCF-based cell fluorescence assay that evaluate the ability of HDL to inhibit LDL oxidation. DE and DE+FA mice significantly impaired the HDL anti-oxidant capacity in comparison with FA mice (p<0.001), as judged by almost a doubling in the level of DCF fluorescence and by a promotion rather than inhibition of oxidation. Decreased HDL anti-oxidant properties were accompanied by reduced anti-inflammatory capacity. The HDL anti-oxidant dysfunction correlated with decreased paraoxonase enzymatic activity, increased levels of plasma 8-isoprostanes, 12-HETE, and 13-HODE. DE also led to increased hepatic levels of ALOX5 mRNA and protein, Glutathione Peroxidase 6 mRNA and 5-HETEs, indicating activation of the 5-lipoxygenase pathway in the liver. Moreover, DE led to enhanced lipid peroxidation in the bronchoalveolar lavage fluid as well.
Conclusions DE emissions induced systemic pro-oxidant effects that led to the development of dysfunctional HDL, which might be one of the mechanisms how air pollution contributes to enhanced atherosclerosis
- © 2013 by American Heart Association, Inc.