Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials

Background: 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 along with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up. Methods: Here, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic patho-biology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (>0.5 mu g/m(3)) and Low (<0.1 mu g/m(3)) inhalable CNT/F exposures in the industrial setting. Peptide biomarker model building and refinement employed linear regression and partial least squared discriminant analyses. Top-ranked peptides were then sequence identified and evaluated for pathological-relevance. Results: In total, 41 peptides were found to be highly discriminatory after model building with a strong linear correlation to personal CNT/F exposure. The top-five peptide model offered ideal prediction with high accuracy (Q(2) = 0.99916). Unsupervised validation affirmed 43.5% of the serum peptidomic variance was 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. Conclusions: The serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks.

Automated summary

In this study, serum peptidome analysis among CNT/F workers identified 41 highly discriminatory peptides that were strongly correlated with CNT/F exposure. The findings suggest that CNT/F exposure may lead to cardiovascular pathology and a pro-thrombotic state among exposed workers.