Linking Polycyclic Aromatic Hydrocarbon Exposure to Cardiometabolic Dysfunction: Evidence from Population Studies and Biological Mechanisms

INTRODUCTION: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse cardiometabolic outcomes. But the molecular mechanism is still unexplored. The purpose of our study is to investigate the relationship between exposure to PAHs and cardiometabolic dysfunction, and to explore the mechanism and molecular pathways. METHODS: We combined National Health and Nutrition Examination Survey (NHANES) data with multiple toxicological databases. Mendelian randomization (MR) was used to evaluate the causal contribution of immune factors to cardiovascular diseases (CVD) and metabolic disorders. Network toxicology and molecular docking were conducted to identify candidate molecular targets and signaling pathways involved in PAHs-related cardiometabolic dysfunction. RESULTS: Higher PAHs exposure was associated with increased cardiometabolic index (CMI) in adults, and this association was partially mediated by monocyte percentage and white blood cell count. MR analyses supported a causal role of these immune-related factors in CVD and metabolic disorders. Network toxicology and molecular docking involved pathways including chemical carcinogenesis-receptor activation, chemical carcinogenesis- DNA adduct formation, cytochrome P450 metabolism, and steroid hormone biosynthesis. CYP1A1, ESR1, and MAO were identified as potential key targets. DISCUSSION: Changes in monocyte percent and white blood count may help explain how PAH exposure is linked to cardiometabolic dysfunction. The implicated pathways and targets provide potential mechanisms. CONCLUSION: Our findings provide epidemiological and mechanistic evidence suggesting that PAH exposure may be linked to adverse cardiometabolic outcomes, potentially through immune-related pathways.