Department of Anatomy and Neurobiology, Virginia Commonwealth University, PO Box 980709, Richmond, VA, 23298, USA.
Division of Field Studies and Engineering, National Institute for Occupational Safety and Health, 1090 Tusculum Avenue, MS-R12, Cincinnati, OH, 45226, USA.
Part Fibre Toxicol. 2021 Oct 28;18(1):39. doi: 10.1186/s12989-021-00431-0.
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.
Here, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (> 0.5 µg/m) and Low (< 0.1 µg/m) 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.
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 = 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.
The serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks.
碳纳米管和纳米纤维（CNT/F）的工业应用日益增多，因此有必要考虑其对人类健康的影响。动物实验表明，CNT/F 可引起肺部、心血管等毒性作用，并使大量生物活性肽释放到血液中，即增强的血清肽组。虽然 CNT/F 工人的流行病学研究报告中急性症状较少，但仍存在对亚临床 CNT/F 效应的担忧，这些效应可能为慢性疾病埋下伏笔，因此需要灵敏的健康结局诊断标志物进行纵向随访。
本研究采用无标记数据非依赖性质谱技术，评估血清肽组作为检测 CNT/F 工人亚临床病理生物学的生物标志物的潜力。研究采用工业环境中高（>0.5μg/m）和低（<0.1μg/m）可吸入 CNT/F 暴露的分层设计。使用线性回归和偏最小二乘判别分析建立和精炼肽生物标志物模型。然后对排名靠前的肽进行序列鉴定，并评估其与病理的相关性。
共发现 41 种肽在模型建立后具有高度的判别能力，与个人 CNT/F 暴露呈强线性相关。前五肽模型具有理想的预测准确性（Q=0.99916）。无监督验证证实，血清肽组学的 43.5%方差归因于 CNT/F 暴露。肽序列鉴定表明，其与血管病理有密切关联。ARHGAP21、ADAM15 和 PLPP3 肽提示高 CNT/F 工人的心血管通透性增加，F13A1、FBN1 和 VWDE 肽提示存在促血栓状态。
血清肽组为 CNT/F 暴露工人的亚临床病理提供了一个诊断窗口，可用于对系统健康风险进行纵向监测。
