Evaluation of gene expression profiling and biochemical response of lung and heart of mice exposed to season fine particulate matter PM2.5

Pathways leading to cardiovascular effects of particulate matter exposure have been linked to oxidative stress, pulmonary and systemic inflammation, endothelial cell dysfunction, atherosclerosis and altered cardiac autonomic function. PM2.5 levels in Milano are greater than those observed in urban sites in Europe, while its chemical composition is similar to those of other European cities. Winter fine particles (PM2.5win) are characterized by the presence of nitrate, organic carbon fraction (with a quite high polycyclic aromatic hydrocarbons content) and elements (Pb, Al, Zn, V, Fe, Cr and others), with a negligible endotoxin content. To elucidate the changes at molecular level, we examined the toxic effects elicited after repeated Milano PM2.5win exposure in BALB/c mice, focusing both on heart and lungs. In the lung parenchyma of PM2.5win-treated mice, ET-1, Hsp70 and cytochromes (Cyp1A1 and Cyp1B1) levels resulted increased, comparing to sham. Within the heart, PM2.5win treatment increased Hsp-70, HO-1 and MPO levels. PM2.5win had a strong impact on global gene expression of heart tissue (181 up-regulated and 178 down-regulated genes) but a less impact on lung global gene expression profiling (14 up-regulated genes and 43 down-regulated genes). Focusing on modulated genes, in lung tissue we found two-three fold changes of those related to polycyclic aromatic hydrocarbons exposure and calcium signalling. In heart tissue the most striking aspect is the twofold to threefold increase in collagen and laminin related genes, together with genes involved in calcium signaling. The current study extends our previous findings, showing that repeated instillations of PM2.5win trigger systemic adverse effect. PM2.5win likely poses an acute threat principally 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.