Title: Fine ambient air particulate matter exposure induces molecular alterations associated with vascular disease progression within plaques of atherosclerotic susceptible mice.
Authors: Floyd, Heather S; Chen, Lung Chi; Vallanat, Beena; Dreher, Kevin
Published In Inhal Toxicol, (2009 Apr)
Abstract: Epidemiology studies have reported associations between increased mortality and morbidity with exposure to particulate air pollution, particularly within individuals with preexisting cardiovascular disease (CVD). Clinical and toxicological studies have provided evidence that exposure to ambient air particulate matter (PM) impacts CVD by increasing plaque size. It is unclear whether PM-induced increased plaque size is associated with molecular disease progression. This study examines molecular profiles within plaques recovered from ApoE(-/-) mice exposed to concentrated ambient air particles (CAPs) to determine whether pulmonary deposition of PM contributes to molecular alterations leading to vascular disease progression. Laser capture microdissection was used to recover atherosclerotic plaques from ApoE(-/-) male mice exposed daily for 5 mo to filtered air or CAPs. Alterations in mRNA expression was assessed in microdissected plaques of CAPs-exposed and air controls using the Affymetrix microarray platform. Bioinformatic analysis indicated alterations in 611 genes: 395 genes downregulated and 216 genes upregulated. Gene ontology revealed CAPs-induced changes to inflammation, proliferation, cell cycle, hematological system, and cardiovascular pathways. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) verified microarray data also revealing gene expression alterations undetected by the microarray analysis, i.e., decreased expression of alpha-actin for smooth muscle cells, and increased expression of the macrophage marker Cd68 and of beta-actin. Comparison of CAPs-induced gene expression profiles demonstrated consistency with previously published gene expression profiles in the ApoE(-/-) mouse model and humans associated with plaque progression. These results indicate that exposure to fine PM induces molecular alterations associated with vascular disease progression and provides insight into potential biological pathways responsible for this effect.
PubMed ID: 19496694
MeSH Terms: Air Pollutants/adverse effects; Animals; Aorta/pathology; Atherosclerosis/etiology*; Atherosclerosis/genetics; Atherosclerosis/pathology*; Disease Models, Animal*; Disease Progression; Genetic Predisposition to Disease*; Inhalation Exposure/adverse effects*; Male; Mice; Mice, Knockout; Particle Size; Particulate Matter/adverse effects*