Air pollutant exposure was associated with elevated serum MMP-7 and MMP-12, which mediated 24.3% of the association between air pollutant mixture and ischemic stroke.
Case-Control (n=200)
Does exposure to air pollution increase the risk of ASCVD through the mediation of DNA methylation and matrix metalloproteinases?
Air pollution-induced ischemic stroke is partially mediated by epigenetic modifications, specifically hypomethylation of the MMP-12 gene and subsequent elevation of MMP-7/12 levels.
Effect estimate: percentage change: 3.8%-12.4% (MMP-7) and 7.7%-19.9% (MMP-12)
Background The biological mechanisms linking air pollution and atherosclerotic cardiovascular disease (ASCVD) remain unclear. This study investigated the mediating roles of DNA methylation and matrix metalloproteinases (MMPs) in this association. Methods A nested case-control study included 200 participants (100 ASCVD cases; 100 matched controls) from the CHCN-BTH cohort study. Serum MMPs and CpG sites methylation were quantified for all subjects. We used generalized linear mixed models (GLMM) to assess the associations between air pollutants and biomarkers, and partial least squares-structural equation modeling (PLS-SEM) to examine the mediation effects. Results The results indicated that an IQR increment of PM 2.5 , PM 10 , PM 1 , and their components (BC, NH₄⁺, NO₃⁻, SO₄²⁻, OM) was significantly associated with elevated serum MMP-7 (percentage change: 3.8%–12.4%) and MMP-12 (7.7%–19.9%). We found that matrix metalloproteinases (MMP-7 and MMP-12) mediated 24.3% of the association between air pollutant mixture (PM 2.5 , PM 10 , and PM 1 ) and ischemic stroke. Furthermore, exposure to PM 2.5 , PM 10 , and PM 1 was associated with significant DNA methylation changes at multiple CpG sites in the MMP-12 gene, especially marked hypomethylation at cg102872409, cg102872497, and cg102872531. Conclusions This study established MMP-7/12 as critical mediators of PM 2.5 –induced ischemic stroke. Hypomethylation at three specific CpG sites in the MMP-12 gene represented pollutant-responsive epigenetic signatures, mechanistically linking air pollution to cardiovascular pathogenesis.
Li et al. (Tue,) conducted a case-control in Atherosclerotic cardiovascular disease (ASCVD) (n=200). Air pollution (PM2.5, PM10, PM1, and components) was evaluated on Serum MMP-7 and MMP-12 levels (percentage change: 3.8%-12.4% (MMP-7) and 7.7%-19.9% (MMP-12)). Air pollutant exposure was associated with elevated serum MMP-7 and MMP-12, which mediated 24.3% of the association between air pollutant mixture and ischemic stroke.