Plasma proteomics analysis reveals sex-related differences in response to diesel exhaust

Abstract

<b>Background:</b> Traffic-related air pollution (TRAP) is a major risk factor of chronic respiratory and cardiovascular disease. Although severity and prevalence of these diseases vary in females and males, sex-related differences of TRAP-mediated protein changes remains unknown. <b>Objective:</b> To examine sex-related differences in plasma profile in response to low, real-world concentrations of diesel exhaust (DE), a paradigm of TRAP. <b>Methods:</b> We used a randomized crossover human controlled exposure study. Male and female (n=5 each) participants (healthy and never-smokers) were exposed to either filtered air (FA) or DE (20,50,150μg PM2.5/m3) for 4 hour (h), with a 4-week washout period between each exposure. Plasma obtained 24h after each exposure was used for proteomics profiling with LC-MS/MS. Data was analysed using linear mixed models to determine the effect of DE on&nbsp;males and females&nbsp;separately, and also infer sex as an effect modifier of DE. <b>Results:</b> Sex-disaggregated data analysis showed that the abundance of 52 proteins in males and 153 proteins in females were significantly altered in plasma following DE exposure, compared to FA. Moreover, sex was a significant effect modifier of 91 DE-related proteins, broadly within functional groups of inflammation, oxidative stress, hemostasis, cardiovascular disease and host defence peptides. Some of these sex effects were concentration dependent, being robust at 150μg PM2.5/m3 of DE. <b>Conclusion:</b> We demonstrate a significant effect of sex on DE-mediated changes in the plasma proteome. This study illustrates that including sex as a modifier of host response to air pollution is essential to gain better insight into pollution-driven biological effects in humans