Circulating metals, leukocyte miRNAs and cardiovascular effects: Potential role of inflammatory and immune-related pathways

Exposure to metals may elicit multiple cardiovascular effects, potentially through inflammation and immune dysregulation. Leukocyte functions are tightly regulated by microRNAs (miRNAs), but their roles in metal-induced cardiovascular effects remain largely unclear. In a panel of 160 Chinese adults, we aim to investigate the cross-sectional association of metal-associated leukocyte miRNAs with 10 cardiovascular indices (including blood pressure, heart rate variability [HRV], and arterial stiffness indices), and further explore whether inflammatory and immune-related pathways may mediate such associations. Of the 55 metal-associated leukocyte miRNAs, 3 miRNAs were significantly associated with blood pressure indices, 3 miRNAs with HRV indices, and 14 miRNAs with arterial stiffness (all P < 0.05). Of note, one nickel-associated miRNA, miR-27a-5p, showed positive associations with both blood pressure and arterial stiffness indices. We further identified 691 inflammatory and immune-related pathways potentially regulated by metal-associated miRNAs, with 7 pathways potentially mediating the associations between metal-associated miRNAs and cardiovascular indices. Notably, two pathways (B-1a B cell differentiation and activation of plasma proteins involved in acute inflammatory response) may mediate the positive associations of miR-27a-5p with blood pressure and with arterial stiffness, respectively. Our study, albeit exploratory, revealed novel associations between metal-associated miRNAs and cardiovascular effects, and identified pathways potentially mediating such associations.