Gold Nanoparticles Compromise TNF-α-Induced Endothelial Cell Adhesion Molecule Expression Through NF-κB and Protein Degradation Pathways and Reduce Neointima Formation in A Rat Carotid Balloon Injury Model.

The aim of this study was to investigate the anti-inflammatory effects and mechanism of action of the gold nanoparticles (AuNPs) on vascular injury. In vitro vascular endothelial cell (EC) inflammation and in vivo rat carotid balloon injury models were used. The expression of TNF-α-induced cell adhesion molecules (CAMs) was suppressed by the AuNPs in human umbilical vein ECs and aortic ECs. The AuNPs reduced TNF-α-induced intracellular ROS production and NF-κB signaling pathways and enhanced CAM protein degradation by increasing their ubiquitination. However, they did not interfere with the mTOR pathway for protein synthesis and TNF-αbinding to ECs. These effects led to a reduction of monocyte adhesion to EC monolayers in vitro and endothelial CAM expression and monocyte/macrophage level in the vascular injured areas, contributing to a substantial decrease of arterial neointima formation in the rat carotid balloon injury model. The serum gold concentration was 99.5±18 ng/ml after three-day oral administration. Moreover, incubation of the AuNPs with serum and albumin led to an increase of particle sizes of the AuNPs. Collectively, we provide the first evidence that demonstrates that AuNPs possess anti-inflammatory bioactivity on vascular ECsin vitro and can reduce arterial neointima hyperplasia during vascular injury in vivo.