Immune biomarkers link air pollution exposure to blood pressure in adolescents

Abstract

Background Childhood exposure to air pollution contributes to cardiovascular disease in adulthood. Immune and oxidative stress disturbances might mediate the effects of air pollution on the cardiovascular system, but the underlying mechanisms are poorly understood in adolescents. Therefore, we aimed to identify immune biomarkers linking air pollution exposure and blood pressure levels in adolescents. Methods We randomly recruited 100 adolescents (mean age, 16 years) from Fresno, California. Using central-site data, spatial-temporal modeling, and distance weighting exposures to the participant’s home, we estimated average pollutant levels [particulate matter (PM), polyaromatic hydrocarbons (PAH), ozone (O3), carbon monoxide (CO) and nitrogen oxides (NOx)]. We collected blood samples and vital signs on health visits. Using proteomic platforms, we quantitated markers of inflammation, oxidative stress, coagulation, and endothelial function. Immune cellular characterization was performed via mass cytometry (CyTOF). We investigated associations between pollutant levels, cytokines, immune cell types, and blood pressure (BP) using partial least squares (PLS) and linear regression, while adjusting for important confounders. Results Using PLS, biomarkers explaining most of the variance in air pollution exposure included markers of oxidative stress (GDF-15 and myeloperoxidase), acute inflammation (C-reactive protein), hemostasis (ADAMTS, D-dimer) and immune cell types such as monocytes. Most of these biomarkers were independently associated with the air pollution levels in fully adjusted regression models. In CyTOF analyses, monocytes were enriched in participants with the highest versus the lowest PM2.5 exposure. In both PLS and linear regression, diastolic BP was independently associated with PM2.5, NO, NO2, CO and PAH456 pollution levels (P ≤ 0.009). Moreover, monocyte levels were independently related to both air pollution and diastolic BP levels (P ≤ 0.010). In in vitro cell assays, plasma of participants with high PM2.5 exposure induced endothelial dysfunction as evaluated by eNOS and ICAM-1 expression and tube formation. Conclusions For the first time in adolescents, we found that ambient air pollution levels were associated with oxidative stress, acute inflammation, altered hemostasis, endothelial dysfunction, monocyte enrichment and diastolic blood pressure. Our findings provide new insights on pollution-related immunological and cardiovascular disturbances and advocate preventative measures of air pollution exposure.

Emerging role of air pollution and meteorological parameters in COVID‐19

“…Monocytes are key white blood cells of the innate immune system and play a central role in inflammasome activation and cardiovascular diseases. Exposure to NO 2 was positively associated with monocyte levels and diastolic blood pressure after full adjustment 106 . Thus NO 2 may promote monocyte enrichment and DNA methylation in monocytes, which subsequently affects diastolic blood pressure and ultimately aggravates COVID‐19.…”

“…87,99 In addition, high-level NO 2 exposure can induce endothelial dysfunction and oxidative stress disturbances. 106 Thus, it is possible that NO 2 exposure contributes to inflammation and immune disorders and exacerbate SARS-COV-2-induced lung damage.…”

“…Exposure to NO 2 was positively associated with monocyte levels and diastolic blood pressure after full adjustment. 106…”

“…After NO 2 exposure, CD11c+ pulmonary cells secreted increased amount of IL‐1α, IL‐1β, IL‐12p70, and IL‐6, and increased Th2 cell activity 104 . In addition, high‐level NO 2 exposure can induce endothelial dysfunction and oxidative stress disturbances 106 . Thus, it is possible that NO 2 exposure contributes to inflammation and immune disorders and exacerbate SARS‐COV‐2–induced lung damage.…”

Physical Activity in Polluted Air—Net Benefit or Harm to Cardiovascular Health? A Comprehensive Review

“…These results are not restricted to adult populations, as indicated by a recent study from Mann et al that indicates that acute increases in traffic related air pollutants were associated with 8-isoprostane levels in 299 children (aged 6–8) [ 22 ]. Likewise, adolescents ( n = 100) were demonstrated to be a susceptible group, by showing that exposure to multiple air pollutants was related to markers of oxidative stress, acute inflammation, altered hemostasis, endothelial dysfunction, monocyte enrichment, and high blood pressure [ 23 ]. In a larger cohort of 3996 subjects, Li et al found acute increases in PM 2.5 and sulfate to be associated with increased C-reactive protein levels, which was also true for nitrogen dioxide (NO 2 ) in the case of interleukin (IL)-6, and for black carbon (BC), sulfate, and ozone (O 3 ) in the case of tumor necrosis factor receptor 2 [ 24 ].…”