Endothelial dysfunction and inflammation induced by iron oxide nanoparticle exposure: Risk factors for early atherosclerosis

• Published in: Toxicology letters Vol. 203; no. 2; pp. 162 - 171
• Main Authors: Zhu, Mo-Tao, Wang, Bing, Wang, Yun, Yuan, Lan, Wang, Hua-Jian, Wang, Meng, Ouyang, Hong, Chai, Zhi-Fang, Feng, Wei-Yue, Zhao, Yu-Liang
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.06.2011; Elsevier
• Subjects: Atheroscelerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - enzymology; Atherosclerosis - etiology; Atherosclerosis - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Adhesion - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Endothelial Cells; Endothelial dysfunction; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Endothelium, Vascular - metabolism; Female; Ferric Compounds - toxicity; Human aortic endothelial cells; Human monocyte; Humans; Intercellular Adhesion Molecule-1 - metabolism; Interleukin-8 - metabolism; Iron oxide nanoparticle; Medical sciences; Metals and various inorganic compounds; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Nanoparticles - toxicity; Nitric Oxide Synthase - metabolism; Phagocytosis - drug effects; Toxicology; U937 Cells; Endothelial dysfunction; Atheroscelerosis; Human aortic endothelial cells; Human monocyte; Iron oxide nanoparticle; Endothelial cell; Nanoparticle; Cardiovascular disease; Oxides; Iron; Ultrafine particle; Epidemiology; Vascular disease; Blood vessel; Atherosclerosis; Aorta; Human; Monocyte; Transition metal; Exposure; Inflammation; Artery; Risk factor; Early; Circulatory system
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2011.03.021

► Iron oxide nanoparticles could induce endothelial cells inflammation and dysfunction. ► Three potential impact pathways. ► Nanoparticles escape from phagocytosis that interact directly with the endothelial monolayer. ► Free iron ions release from nanoparticles and thus impact the endothelial cells. ► Nanoparticles are phagocytized by monocytes to provoke oxidative stress responses. More recently, the correlation between exposure to nanoparticles and cardiovascular diseases is of particular concern in nanotoxicology related fields. Nanoparticle-triggered endothelial dysfunction is hypothesized to be a dominant mechanism in the development of the diseases. To test this hypothesis, iron oxide nanoparticles (Fe 2O 3 and Fe 3O 4), as two widely used nanomaterials and the main metallic components in particulate matter, were selected to assess their potential risks on human endothelial system. The direct effects of iron oxide nanoparticles on human aortic endothelial cells (HAECs) and the possible effects mediated by monocyte (U937 cells) phagocytosis and activation were investigated. In the study, HAECs and U937 cells were exposed to 2, 20, 100 μg/mL of 22-nm-Fe 2O 3 and 43-nm-Fe 3O 4 particles. Our results indicate that cytoplasmic vacuolation, mitochondrial swelling and cell death were induced in HAEC. A significant increase in nitric oxide (NO) production was induced which coincided with the elevation of nitric oxide synthase (NOS) activity in HAECs. Adhesion of monocytes to the HAECs was significantly enhanced as a consequence of the up-regulation of intracellular cell adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) expression, all of which are considered as early steps of atheroscelerosis. Phagocytosis and dissolution of nanoparticles by monocytes were found to simultaneously provoke oxidative stress and mediate severe endothelial toxicity. We conclude that intravascular iron oxide nanoparticles may induce endothelial system inflammation and dysfunction by three ways: (1) nanoparticles may escape from phagocytosis that interact directly with the endothelial monolayer; (2) nanoparticles are phagocytized by monocytes and then dissolved, thus impact the endothelial cells as free iron ions; or (3) nanoparticles are phagocytized by monocytes to provoke oxidative stress responses.