Association of PM2.5-bound multiple metals co-exposure with early cardiovascular damage: A panel study in young adults combing metabolomics

The association of individual metals in PM_2.5 with cardiovascular damage has been established in previous studies, but there are fewer studies on co-exposure to multiple metals and potential metabolic alterations in cardiovascular damage. To investigate the early cardiovascular effects of multiple metals and the mediating effects of metabolites, we conducted a panel study on young adults from 2017 Winter to 2018 Autumn in Caofeidian, China. A total of 180 serum samples were analyzed for metabolomic profiles using liquid chromatography-mass spectrometry. The associations between personal metal exposure, metabolite levels, and indicators of cardiovascular injury were analyzed by linear mixed-effects modeling (LEM) and Bayesian kernel machine regression (BKMR). Metabolomic analyses showed 79 metabolites in the serum of healthy adults changed significantly between seasons and all metabolites were strongly associated with toxic metals. Additionally, differential metabolites were enriched in seven metabolic pathways and activated by metal exposure, such as Butanoate metabolism and Linoleic acid metabolism. BKMR model interpreted that the overall effect of metals mixture was negatively associated with Capryloyl glycine and Sphinganine and Sb mainly contributed to the effect. The results of mediation analysis revealed that the association between V and VEGF was mediated by Diethylhexyl with a partial proportion of 13.4%. Furthermore, the result also found the association between CerP(d18:1/26:1(17Z)) and ET-1 was mediated by TGFβ1 with a proportion of 53.4%. Our findings suggested that multiple metal exposure was associated with metabolomic changes of cardiovascular damage in young adults, and may simultaneously affect the metabolomic changes by inducing oxidative stress and inflammation.