Defining the effects of traffic-related air pollution on the human plasma proteome using an aptamer proteomic array: A dose-dependent increase in atherosclerosis-related proteins

Environ Res. 2022 Jun;209:112803. doi: 10.1016/j.envres.2022.112803. Epub 2022 Feb 1.


Background: Traffic-related air pollution (TRAP) is a critical risk factor and major contributor to respiratory and cardiovascular disease (CVD). The effects of TRAP beyond the lungs can be related to changes in circulatory proteins. However, such TRAP-mediated changes have not been defined in an unbiased manner using a controlled human model.

Objective: To detail global protein changes (the proteome) in plasma following exposure to inhaled diesel exhaust (DE), a paradigm of TRAP, using controlled human exposures.

Methods: In one protocol, ex-smokers and never-smokers were exposed to filtered air (FA) and DE (300 μg PM2.5/m3), on order-randomized days, for 2 h. In a second protocol, independent never-smoking participants were exposed to lower concentrations of DE (20, 50 or 150 μg PM2.5/m3) and FA, for 4 h, on order-randomized days. Each exposure was separated by 4 weeks of washout. Plasma samples obtained 24 h post-exposure from ex-smokers (n = 6) were first probed using Slow off-rate modified aptamer proteomic array. Plasma from never-smokers (n = 11) was used for independent assessment of proteins selected from the proteomics study by immunoblotting.

Results: Proteomics analyses revealed that DE significantly altered 342 proteins in plasma of ex-smokers (n = 6). The top 20 proteins therein were primarily associated with inflammation and CVD. Plasma from never-smokers (n = 11) was used for independent assessment of 6 proteins, amongst the top 10 proteins increased by DE in the proteomics study, for immunoblotting. The abundance of all six proteins (fractalkine, apolipoproteins (APOB and APOM), IL18R1, MIP-3 and MMP-12) was significantly increased by DE in plasma of these never-smokers. DE-mediated increase was shown to be concentration-dependent for fractalkine, APOB and MMP-12, all biomarkers of atherosclerosis, which correlated with plasma levels of IL-6, a subclinical marker of CVD, in independent participants.

Conclusion: This investigation details changes in the human plasma proteome due to TRAP. We identify specific atherosclerosis-related proteins that increase concentration-dependently across a range of TRAP levels applicable worldwide.

Keywords: Air pollution; Atherosclerosis; Biomarkers; Diesel exhaust; Proteomics.

MeSH terms

  • Air Pollutants* / analysis
  • Air Pollutants* / toxicity
  • Air Pollution* / adverse effects
  • Air Pollution* / analysis
  • Atherosclerosis* / chemically induced
  • Atherosclerosis* / etiology
  • Atherosclerosis* / metabolism
  • Humans
  • Proteome
  • Proteomics
  • Random Allocation
  • Vehicle Emissions / analysis
  • Vehicle Emissions / toxicity


  • Air Pollutants
  • Proteome
  • Vehicle Emissions