A potential strategy for in-stent restenosis: Inhibition of migration and proliferation of vascular smooth muscle cells by Cu ion

The in-stent restenosis (ISR) often happens after the implantation of metal stents, including both bare metal stents (BMSs) and drug-eluting stents (DESs). Drug release from DESs could reduce significantly the occurrence of ISR but also suppress the revascularization and cause thrombosis. In this study, the effect of Cu ion in a range of 0 to 500 mu M on the migration and proliferation of rat aortic smooth muscle cells (RASMCs) was investigated by a series of in vitro experiments including wound-healing assay, cell viability assay and flow cytometric analysis. It has been found that the critical concentration of Cu ion should be at least 250 mu M in order to significantly inhibit the migration of RASMCs and the proliferation of RASMCs were impeded by every dose of Cu ion used in this study. In addition, the protein level of caspase-3 was upregulated by 250 mu M and 500 mu M Cu2+ exposure, which might be the main reason for RASMCs apoptosis. Thus, it is proposed that ISR might be prevented by the constant release of Cu ion.