Aggravation of atherosclerosis by pulmonary exposure to indium oxide nanoparticles

The use of indium oxide (In₂O₃) and indium-metal hybrids for various applications, including the manufacture of batteries and liquid crystal displays, increases the chances of human exposure to In₂O₃ via inhalation, especially in occupational settings. However, there is little information available on the toxic effects of In₂O₃ nanoparticles (NPs) on secondary organs following pulmonary exposure. In this study, we evaluated the effect of In₂O₃ NPs on atherosclerotic plaque formation and the related mechanisms after pulmonary exposure in low-density lipoprotein receptor knockout (Ldlr^-/-) mice. At 10 weeks after a single pharyngeal aspiration, In₂O₃ NPs caused chronic active inflammation, pulmonary alveolar proteinosis, and accumulation of inflammatory cells in the peribronchial and perivascular areas of the lungs. The expression of pro-inflammatory cytokines in the lung tissue, including TNF-α and MCP-1, was markedly increased by treatment with In₂O₃ NPs. In the In₂O₃ NP-treated groups, the levels of total cholesterol and low-density lipoprotein in the plasma were increased, whereas HDL cholesterol showed no significant changes compared to vehicle control. The formation of atherosclerotic lesions was increased by treatment with In₂O₃ NPs. Real-time PCR analysis of the aorta showed that IL-6 and MCP-1 expression was up-regulated upon treatment with In₂O₃ NPs. These results suggested that the pulmonary inflammation induced by In₂O₃ NPs aggravates the progression of atherosclerotic plaque formation, possibly by the alteration of the plasma lipid profile and enhancement of the aortic inflammatory processes.