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Title: Hypercholesterolemia potentiates aortic endothelial response to inhaled diesel exhaust.

Authors: Maresh, J Gregory; Campen, Matthew J; Reed, Matthew D; Darrow, April L; Shohet, Ralph V

Published In Inhal Toxicol, (2011 Jan)

Abstract: BACKGROUND: Inhalation of diesel exhaust induces vascular effects including impaired endothelial function and increased atherosclerosis. OBJECTIVE: To examine the in vivo effects of subchronic diesel exhaust exposure on endothelial cell transcriptional responses in the presence of hypercholesterolemia. METHODS: ApoE (-/-) and ApoE (+/+) mice inhaled diesel exhaust diluted to particulate matter levels of 300 or 1000 μg/m³ vs. filtered air. After 30 days, endothelial cells were harvested from dispersed aortic cells by fluorescent-activated cell sorting (FACS). Relative mRNA abundance was evaluated by microarray analysis to measure strain-specific transcriptional responses in mice exposed to dilute diesel exhaust vs. filtered air. RESULTS: Forty-nine transcripts were significantly dysregulated by >2.8-fold in the endothelium of ApoE (-/-) mice receiving diesel exhaust at 300 or 1000 μg/m³. These included transcripts with roles in plasminogen activation, endothelial permeability, inflammation, genomic stability, and atherosclerosis; similar responses were not observed in ApoE (+/+) mice. CONCLUSIONS: The potentiation of diesel exhaust-related endothelial gene regulation by hypercholesterolemia helps to explain air pollution-induced vascular effects in animals and humans. The observed regulated transcripts implicate pathways important in the acceleration of atherosclerosis by air pollution.

PubMed ID: 21222557 Exiting the NIEHS site

MeSH Terms: Air Pollutants/toxicity*; Air Pollution/adverse effects; Animals; Aorta/metabolism; Atherosclerosis/physiopathology; Endothelium, Vascular/physiopathology*; Gene Expression Regulation; Hypercholesterolemia/metabolism*; Inflammation/physiopathology; Inhalation Exposure*; Male; Mice; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Particulate Matter/toxicity*; Vehicle Emissions/toxicity*

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