Endothelial cell injury and dysfunction induced by silver nanoparticles through oxidative stress via IKK/NF-κB pathways.

Abstract

Epidemiological studies have indicated that particulate matter (PM) exposure is most likely relevant to atherosclerosis. Endothelial cell injury and dysfunction are considered the early events in the initiation of atherosclerosis. Silver nanoparticles (AgNPs), with a smaller size and higher reactive activity, may induce much higher toxicity to endothelial cells compared with PM. However, few studies have been performed to determine the effect of AgNPs on endothelial cells. In the present study, human umbilical vein endothelial cells (HUVECs) were chosen as model cells to systematically explore the toxicity of AgNPs to endothelial cells. The obtained results indicated that exposure to AgNPs could inhibit proliferation, damage the cell membrane and seriously induce apoptosis. Simultaneously, the inflammatory cytokines, adhesion molecules, and chemokines of HUVECs were clearly up-regulated, which resulted in the adhesion of many monocytes to endothelial cells. More importantly, we found that dysfunctions of endothelial cells could be ascribed to the activation of NF-κB pathways. Furthermore, an oxidation inhibitor, N-acetyl-l-cysteine (NAC), effectively antagonized all of the AgNPs-induced responses, which indicated the key role of ROS production during the exposure of AgNPs in the toxicity of endothelial cells. In summary, our results clearly demonstrated that AgNPs could induce the injury and dysfunction of HUVECs through the activation of IKK/NF-κB, which is associated with oxidative stress, suggesting that exposure to AgNPs may be a potential hazardous factor for early atherosclerosis.