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.

Endothelial inflammatory transcriptional responses to an altered plasma exposome following inhalation of diesel emissions

“…Genes spanning all three gene clusters from this analysis including TLR8 , COL11A1 , and LTBP3 ( Figure 5C ) were previously associated in other studies ranging from smoking, ozone, particulate matter, asthma, and chronic obstructive pulmonary disease (Konigshoff, Kneidinger et al 2009, Shi, Chen et al 2009, Bauer, Diaz-Sanchez et al 2012, Bezemer, Sagar et al 2012, Sancini, Farina et al 2014). The identification of extracellular signaling molecules within each cluster suggest a dynamic role for the extracellular matrix and the regulation of secretory molecules in response to diesel exposure.…”

The involvement of Nox4 in fine particulate matter exposure-induced cardiac injury in mice

“…In addition, PAHs are also suggested to be associated with CVD (Baxter et al, 2014). It has been reported that PM 2.5 with a small size can penetrate deeply into the alveolar regions of the lung and even transmit through blood into the circulation, including the heart, and then triggers cardiovascular effects (Guarnieri and Balmes, 2014;Sancini et al, 2014). Our data showed that PM 2.5 exposure results in lung inflammation and injury, which may further cause cardiovascular effects and then lead to cardiac injury.…”

Prolonged Exposure to Traffic-related Particulate Matter Showed Distinct Molecular Mechanisms of Lung Injury in Rats

“…The in ltration of PM in lung is known to disrupt the cell membrane integrity and subsequently increase the intracellular calcium ion (Ca 2+ ) concentration. The calcium signaling affects a broad spectrum of cellular functions such as motility, metabolism, cell growth, proliferation and apoptosis (35) and the dysregulation of intracellular Ca 2+ has been reported to associate with PM-induced oxidative stress and in ammation in human lung broblast cells (36), pulmonary artery endothelium cells (37), and mouse lungs (38). Proteins that control e ux and in ux of calcium stand important roles in calcium homeostasis.…”