Mitochondrial DNA methylation as a bridge: Linking indoor air purification to alleviated cardiovascular impairments in young adults.

Current research on fine particulate matter (PM2.5) has yet to fully clarify its impact on mitochondrial function and cardiovascular health through epigenetic pathways. To investigate these associations, 38 healthy young adults were recruited into a randomized double-blind crossover trial. We measured methylation levels at mtDNA CpG sites, blood pressure, and 16 cardiovascular indicators. Linear mixed-effect model was employed to analyze the exposure-mtDNA methylation relationship, followed by mediation analyses to explore whether mtDNA methylation serves as a mediator linking PM2.5 exposure to cardiovascular alterations. The air purifier intervention resulted in a 47.45% reduction in indoor PM2.5 levels. We observed a significant association between increased PM2.5 exposure and reduced mtDNA methylation. Specifically, each 10-μg/m3 rise in personal PM2.5 level at lag 24-48h was correlated with hypomethylation in the mtATP6 gene. Mediation analysis further suggested that mtDNA hypomethylation may partially mediate the associations between PM2.5 exposure and several cardiovascular parameters. For instance, its hypomethylation of mtDNA mediated 14.87% (P = 0.04) of the impact of PM2.5 on D-dimer levels at lag 0h, illustrating a clear epigenetic pathway from pollution exposure to cardiovascular impairment. Our study demonstrates that PM2.5 exposure leads to mtDNA hypomethylation, an epigenetic change that mediates the association with adverse cardiovascular indicators. These findings implicate mitochondrial epigenetic dysregulation as a statistical mediator and are suggestive of mtDNA methylation as a potential target for interventions against pollution-related cardiovascular impact.