title: Health risk assessment for air pollutants: alterations in lung and cardiac gene expression in mice exposed to Milano winter fine particulate matter (PM2.5).
abstract: Oxidative stress, pulmonary and systemic inflammation, endothelial cell dysfunction, atherosclerosis and cardiac autonomic dysfunction have been linked to urban particulate matter exposure. The chemical composition of airborne pollutants in Milano is similar to those of other European cities though with a higher PM2.5 fraction. Milano winter fine particles (PM2.5win) are characterized by the presence of nitrate, organic carbon fraction, with high amount of polycyclic aromatic hydrocarbons and elements such as Pb, Al, Zn, V, Fe, Cr and others, with a negligible endotoxin presence. In BALB/c mice, we examined, at biochemical and transcriptomic levels, the adverse effects of repeated Milano PM2.5win exposure in lung and heart. We found that ET-1, Hsp70, Cyp1A1, Cyp1B1 and Hsp-70, HO-1, MPO respectively increased within lung and heart of PM2.5win-treated mice. The PM2.5win exposure had a strong impact on global gene expression of heart tissue (181 up-regulated and 178 down-regulated genes) but a lesser impact on lung tissue (14 up-regulated genes and 43 down-regulated genes). Focusing on modulated genes, in lung we found two- to three-fold changes of those genes related to polycyclic aromatic hydrocarbons exposure and calcium signalling. Within heart the most striking aspect is the twofold to threefold increase in collagen and laminin related genes as well as in genes involved in calcium signaling. The current study extends our previous findings, showing that repeated instillations of PM2.5win trigger systemic adverse effects. PM2.5win thus likely poses an acute threat primarily to susceptible people, such as the elderly and those with unrecognized coronary artery or structural heart disease. The study of genomic responses will improve understanding of disease mechanisms and enable future clinical testing of interventions against the toxic effects of air pollutant.
authors.affiliation: Department of Health Science, POLARIS Research Center, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Sancini
authors.affiliation: Department of Health Science, POLARIS Research Center, University of Milano-Bicocca, Monza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Farina
authors.affiliation: Department of Medical Biotechnologies and Translational Medicine (BIOMETRA), Università degli Studi di Milano, Segrate, Italy; Institute of Biomedical Technology, CNR, Segrate, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Battaglia
authors.affiliation: Institute of Biomedical Technology, CNR, Segrate, Italy.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Cifola
authors.affiliation: Institute of Biomedical Technology, CNR, Segrate, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mangano
authors.affiliation: Department of Environmental Science, POLARIS Research Center, University of Milano-Bicocca, Milano, Italy.
authors.forename: Paride
authors.initials: P
authors.lastname: Mantecca
authors.affiliation: Department of Environmental Science, POLARIS Research Center, University of Milano-Bicocca, Milano, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Camatini
authors.affiliation: Department of Health Science, POLARIS Research Center, University of Milano-Bicocca, Monza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Palestini
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D063990:Gene Ontology; D006262:Health; D006321:Heart / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D018570:Risk Assessment; D012621:Seasons; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter