Serum Proteoglycan Alterations Associated with Cardiovascular Risk in Pb-Battery Recycling Workers Using Exploratory...

Lead (Pb) is a prevalent environmental and occupational toxin that disrupts several biological systems. Its toxicological effects are well known but serum proteomic alterations associated with Pb remain insufficiently characterized. This study investigated serum proteomic changes in Pb-battery recycling workers (Pb-BRW) to identify the candidate proteins associated with Pb exposure using high-resolution mass spectrometry (HRMS). Blood samples (5 mL) were collected from Pb-BRW (n = 78) and age-matched unexposed controls (n = 65) from three industries in Karnataka, India. Blood Pb levels were assessed using inductively coupled plasma-optical emission spectroscopy. Serum samples (n = 10) pooled from each group were analyzed using quantitative discovery HRMS. Data are available via ProteomeXchange with identifier PXD082567. Raw files were processed using Proteome Discoverer, and proteins were identified using the UniProt Homo sapiens reviewed database. Further data were analysed in Perseus with log₂ transformation and imputation. Gene ontology was used for functional enrichment analysis. Candidate proteins were selected (nominal p < 0.05 and |log₂FC| ≥ 1.2) as exploratory filtering criteria and visualized using a volcano plot and heatmap. Selected proteins were further validated using ELISA in an independent set of serum samples obtained from Pb-BRW (n = 68) and control subjects (n = 55). A total of 257 serum proteins were identified. Exploratory HRMS-based proteomic profiling identified 26 candidate proteins with nominal p < 0.05. Functional enrichment analysis suggested associations with cardiovascular-related processes. Of these, eight candidate proteins met both exploratory filtering criteria, including five showing higher and three showing lower abundance in Pb-BRW. Lumican (LUM) and Proteoglycan-4 (PRG4) were selected for ELISA-based validation based on their abundance patterns and biological relevance to extracellular matrix organisation and vascular homeostasis. Exploratory serum proteomic profiling revealed alterations in proteins involved in lipid transport and extracellular matrix organization in Pb-BRW. The identification and independent validation of LUM and PRG4 suggest their potential as candidate biomarkers associated with Pb-related cardiovascular alterations.