Naked physically synthesized gold nanoparticles affect migration, mitochondrial activity, and proliferation of vascular smooth muscle cells.

Abstract

IntroductionVascular smooth muscle cells (VSMCs) play an important role in the development and progression of atherosclerosis and vascular injuries in terms of proliferation and migration. Therefore, the aim of this study was to investigate the anti-migratory and proliferative effects of naked gold nanoparticles (AuNPs) on VSMCs.Materials and methodsOne set of physically synthesized AuNPs (pAuNPs) and three sets of chemically synthesized AuNPs (cAuNPs) were tested.Results and discussionAmong them, the pAuNPs were found to significantly and markedly inhibit platelet-derived growth factor (PDGF)-induced VSMC migration. Transmission electron microscopy revealed that the pAuNPs were ingested and aggregated in the cytoplasm at an early stage of treatment, while the viability of VSMCs was not affected within 24 hours of treatment. The pAuNP treatment enhanced cellular mitochondrial activity but inhibited basal and PDGF-induced VSMC proliferation, as determined by MTT, WST-1, and BrdU cell proliferation assays. Furthermore, the pAuNPs did not interfere with PDGF signaling or matrix metalloproteinase-2 expression/activity. Unlike the cAuNPs, the pAuNPs could markedly reduce VSMC adhesion to collagen, which was supported by the findings that the pAuNPs could inhibit collagen-induced tyrosine protein and focal adhesion kinase (FAK) phosphorylation and actin cytoskeleton reorganization during cell adhesion. The in vitro effects of the pAuNPs were confirmed in the in vivo rat balloon-injured carotid artery model by diminishing the proliferating VSMCs.ConclusionTaken together, the present study provides the first evidence that naked pAuNPs can reduce VSMC migration and compromise cell adhesion by affecting FAK and tyrosine-protein activation. The pAuNPs also have an inhibitory effect on PDGF-induced VSMC proliferation and can reduce proliferating/migrating VSMC expression in vivo.