Air pollution and hypertension in rural versus urban children: Lipidomic insights into PM2.5 impacts.

Fine particulate matter and its impact on blood pressure (BP) in children remain a concern, with the role of lipid metabolism as a potential mediator not fully elucidated. We conducted a cohort study of 2239 urban subjects and 2194 rural subjects at baseline in China from 2014 to 2024 and a nested case-control study with lipidomics analyses. Analysis results showed that higher fine particulate matter smaller than 2.5 μm (PM2.5) exposure associated with high density lipoprotein cholesterol (HDL-C), non-HDL-C, and higher systolic blood pressure (SBP), partially mediated by HDL-C/non-HDL-C changes. Mediation analysis indicated a significant mediating effect of HDL-C on the PM2.5-DBP and PM2.5-MAP (DBP, diastolic blood pressure; MAP, mean arterial pressure) association in urban subjects, while no mediation effect was found in rural subjects. For non-HDL-C, significant mediating effects were observed in both urban and rural subjects. Further analyses revealed distinct urban-rural lipidomic patterns, with specific phosphatidylethanolamine (PEs) mediating PM2.5-related hypertension in rural subjects, while lactosylceramides (LacCer) played this role in urban youth. These patterns extended to other BP indices as well. In the urban area, PG(44:11), LacCer(d45:1), were identified as playing significant mediating roles in the association between PM2.5 exposure and hypertension while for rural subjects, PEs including PE(16:0/16:0) and PE(18:0/18:2) showed significant mediating effects. Our findings underscore the impact of PM2.5 exposure on lipid profiles and BP risk in children, suggesting area-specific mechanisms and the potential for lipidomic-based interventions to mitigate environmental health risks.