Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells

Abstract

Air pollutant effects on endothelial cells <p>Gene expression analysis of human microvascular endothelial cells exposed to diesel exhaust particles and oxidized phospholipids revealed several upregulated gene modules, including genes involved in vascular inflammatory processes such as atherosclerosis.</p> Abstract Background: Ambient air pollution is associated with increased cardiovascular morbidity and mortality. We have found that exposure to ambient ultrafine particulate matter, highly enriched in redox cycling organic chemicals, promotes atherosclerosis in mice. We hypothesize that these prooxidative chemicals could synergize with oxidized lipid components generated in low-density lipoprotein particles to enhance vascular inflammation and atherosclerosis.

Potential Health Impact of Nanoparticles

“…Potentially safe NPs (such as carbon black and polystyrene) induced either no response or only a tier 1 response, whereas potentially hazardous NPs (such as metal oxides and ambient UFP) induce proinflammatory (tier 2) or cytotoxic (tier 3) effects. We have also shown for ambient air pollution particles that one can link the hierarchical oxidative stress paradigm to the in vivo outcomes in animal disease models, as reviewed above (2,18).…”

“…Because the atherosclerotic plaque is basically a chronic inflammatory lesion, there may be synergy between the PMinduced inflammation and the prooxidative and proinflammatory effects of oxidized low density lipoprotein (LDL). We have demonstrated through a genome-wide analysis that oxidized LDL components synergize with organic DEP chemicals in stimulating the expression of oxidative stress-responsive genes (18).…”

Air Pollution Exposures and Circulating Biomarkers of Effect in a Susceptible Population: Clues to Potential Causal Component mixtures and mechanisms

“…Stronger associations during the cooler phase of study, despite similar PM 0.25 mass concentrations in cooler and warmer phases, further support the view that the greatest impacts on systemic responses may be attributable to nanoparticles not adequately represented by the present par ticle mass measurements as well as to unmea sured toxic air pollutants that increase near ground level in the winter. Our related experi mental work using particles collected in the LA air basin at the Southern California Particle Center suggests that this might include redox active and electrophilic organic components of traffic exhaust particles in the ultrafine range (Araujo et al 2008;Gong et al 2007;Li et al 2003;Ntziachristos et al 2007;Shinyashiki et al 2008).…”

Endothelial cell regulation by phospholipid oxidation products

“…7 This latter effect appears to be due to activation of neutral sphingomyelinase, which has been demonstrated to alter caveolar function. 37 While Ox-PAPC inhibits LPS effects on inflammation, it is actually synergistic with effects of fine diesel exhaust particles found as air-pollutants 38 and with TNF alpha. 37 The mechanisms regulating these synergisms are not yet known.…”