Semi- and intermediate-volatility organic compounds (S/IVOCs), primarily emitted from combustion processes, contribute significantly to secondary organic aerosol (SOA) formation, yet their vascular toxicity remains underexplored. Here, we quantified 36 SVOCs and 40 IVOCs in particulate matter with an aerodynamic diameter of less than 2.5 microns (PM2.5) samples from household solid fuel combustion on the Tibetan Plateau and the Guanzhong Plain, assessing their cytotoxicity on human vascular smooth muscle cells (VSMCs). Combustion on the Tibetan Plateau yielded higher proportions of IVOCs (e.g., 19.90 % in bitumite heating [BH] vs. 16.17 % in BH from the plain; p < 0.05), likely due to hypoxia conditions at high altitude, which correspondingly exhibited greater cytotoxicity. Inflammation was identified as the primary pattern of PM₂.₅-induced toxicity. Western blot analysis revealed altered expression of p62/LC3-II/I and dose-dependent variations in p-mTOR/p-PI3K/p-Akt proteins (a master regulator of cell growth and autophagy), indicating S/IVOCs-induced disruption of the autophagy pathway. Correlation and statistical analyses confirmed a strong association between S/IVOCs and autophagy flux (a cellular 'self-cleaning' process) proteins. Molecular docking further demonstrated that key toxic S/IVOCs (e.g., 1,6-dinitropyrene, β-tridecane) directly compete with ATP for binding to autophagy-regulating proteins, leading to autophagy dysregulation. These findings highlight the role of high-altitude hypoxia in shaping S/IVOCs emissions and their potential vascular toxicity, emphasizing the urgent need for clean energy transitions in high-altitude regions vulnerable to solid fuel pollution.
Keywords: Autophagy flux; S/IVOC; Solid fuel combustion; Tibet Plateau; Vascular toxicity.
Copyright © 2025 Elsevier B.V. All rights reserved.