Mass spectrometry-based metabolomics and lipidomics analysis for potential biomarkers of cardiovascular disorders associated with ambient fine particulate matter exposure

Air pollution is a worldwide environmental problem. Ambient fine particulate matter with a diameter less than 2.5μm (PM2.5) is a key indicator of air pollution and one of the most critical air contaminants. PM2.5 is a combined pollutant with multiple sources. Nearly all individuals may be exposed to PM2.5 particles. Epidemiological and toxicological studies have shown that PM2.5 exposure is associated with exacerbation and development of cardiovascular disease. PM2.5 from combustion source has been found to cause increased mortality risk for cardiovascular disease. However, the mechanisms of PM2.5 effects on cardiovascular system remain uncertain. Mass spectrometry (MS)-based metabolomics and lipidomics are powerful tools for the revelation of molecular mechanisms by analyzing the endogenous metabolites in biological samples. In this project, animal and cell models will be established to study the cardiovascular disorders associated with PM2.5 exposure. Untargeted metabolomics and lipidomics approaches will be conducted to identify potential biomarkers in rat plasma and heart tissues, as well as in human cardiac cells. Targeted analysis will be performed to quantify the identified biomarkers in specific metabolic pathways and networks. Imaging metabolomics will be used to reveal the localization and spatial distribution of the metabolites in rat heart tissues. Because polycyclic aromatic hydrocarbons (PAHs) and their derivatives in PM2.5 particles are suspected to be positively associated with cardiovascular disease, we will also detect levels of the contaminants in PM2.5 particles and biological samples. Correlation analysis will be conducted among the pollutant contents, animal physiological indicators, and biomarker levels. The toxicity mechanisms about PM2.5-induced cardiovascular disorders will be proposed and biologically verified. We believe this research will be an important step towards the understanding of molecular mechanisms of cardiovascular disorders associated with PM2.5 exposure, providing valuable scientific basis for human health risk assessments about air pollution.