Identification of lead-binding proteins as carriers and potential molecular targets associated with systolic blood pressure

Lead (Pb) exposure is well recognized as a significant environmental factor associated with the high incidence of cardiovascular diseases. However, the carriers and molecular targets of Pb in human blood remain to be understood, especially for a real Pb exposure scenario. In this study, a total of 350 blood samples were collected from the smelting workers and systematically analyzed using metallomics and metalloproteomics approaches. The results showed that the majority of Pb (∼99.4%) could be presented in the blood cells. Pb in the cytoplasm of blood cells accounted for approximately 83.1% of the total blood Pb, with nearly half of Pb being bound to proteins. Pb-binding proteins in the blood of workers were identified as hemoglobin, catalase, haptoglobin, δ-aminolevulinic acid dehydratase, and peroxiredoxin-2. Multiple linear regression analysis demonstrated that higher levels of Pb bound to proteins (Mix-bound Pb and Protein-bound Pb) were positively associated with higher systolic blood pressure (p 0.05). This study suggested that Pb bound to proteins could be a suitable biomarker for indicating the potential risk of occupational hypertension. [Display omitted] •99.4% of Pb was concentrated in blood cells of workers, and primarily (83.1%) existed in cytoplasm, the distribution patterns of Pb in the blood was affected by workplaces.•Pb selectively bound to proteins in blood cells of workers, including hemoglobin, catalase, haptoglobin, δ-aminolevulinic acid dehydratase, and peroxiredoxin-2.•Protein-bound Pb is an earlier and more sensitive indicator than blood lead levels, as it is positively correlated with systolic blood pressure, indicating the risk of hypertension.