Occupational Dust Exposure is Associated with Cardiovascular Risk via Glycerophospholipid Metabolism and IL-6-Mediated Endothelial Inflammation: Insights from Multi-Omics Integration.

Abstract

Occupational dust is a widespread environmental contaminant associated with cardiovascular disease risk, yet its underlying molecular mechanisms remain insufficiently elucidated. This study investigated the associations between occupational respirable dust exposure (CDE) and early indicators of cardiovascular risk in 8662 participants from the China-Northern Anhui Coal Workers Cohort (C-NACWC). To explore potential mechanisms, we employed an integrative multi-omics approach, combining serum lipidomics from these participants with publicly available single-cell RNA sequencing data (GSE159677) from human atherosclerotic plaques. Higher levels of CDE were associated with an elevated cardiovascular risk score (CVRS) and adverse lipid profiles. Lipidomics analysis revealed that glycerophospholipid metabolism and insulin resistance mediated 8-21% of the associations between CDE and both CVRS and triglyceride. Single-cell RNA sequencing analysis showed that differentially expressed genes were significantly enriched in glycerophospholipid metabolism and inflammation-related pathways within the atherosclerotic microenvironment. Multi-omics integration suggested interleukin-6 (IL-6) as a potential hub gene in endothelial cells, highlighting a potential link between metabolic dysregulation and inflammatory signaling. Consistently, CDE was positively associated with serum IL-6 concentrations in these miners. Our findings suggest a potential pathway whereby occupational dust exposure is associated with increased early cardiovascular risk via glycerophospholipid metabolism and insulin resistance, which is linked to IL-6- related endothelial inflammation. These findings provide a scientific basis for integrating inflammatory biomarkers into routine occupational screenings. Furthermore, they advocate for a shift in occupational health policy toward comprehensive cardiovascular risk monitoring and personalized health management in dust-exposed populations.