Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals, with significant augmentation of bioactive circulating peptides, the serum peptidome. While epidemiology among CNT/F workers reports few acute symptoms, there remains concern that CNT/F may prime for chronic disease. Here, the serum peptidome is assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Using a stratified design between High (>0.5 ug/m3) and Low (<0.1 ug/m3) CNT/F exposures, 2,726 serum peptides significantly distinguish the groups. Of these, 41 are found to be highly discriminatory after model building and exhibit a strong linear correlation with personal CNT/F exposures. The top-five peptide model offers ideal prediction with high accuracy (Q2=0.99916). Unsupervised validation affirms 43.5% of the serum peptidomic variance is attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers. The serum peptidome affords a diagnostic window into pre-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring health risks.
[doi:10.25345/C5RV4G]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: carbon nanotubes ; biomarkers ; peptidomics ; vascular ; health outcomes
Principal Investigators: (in alphabetical order) |
Andrew K Ottens, Virginia Commonwealth University, United States |
Submitting User: | akottens |
Mostovenko E, Dahm MM, Schubauer-Berigan MK, Eye T, Erdely A, Young TL, Campen MJ, Ottens AK.
Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials.
Part Fibre Toxicol. 2021 Oct 28;18(1):39. Epub 2021 Oct 28.
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