Aggravation of atherosclerosis by pulmonary exposure to indium oxide nanoparticles

Abstract

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-alpha 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.