Small interfering RNA targeting c-myc inhibits vein graft restenosis in rats

Objective Persistent high expression of the c-myc gene after vein transplantation may lead to intimal hyperplasia and restenosis of the grafted veins.The present study aims to evaluate the effect of locally administrated small interfering RNA(siRNA) targeting the c-myc gene on intimal hyperplasia after vein autotransplantation.Methods We performed autologous jugular vein to carotid artery reverse interposition on 32 male SD rats,which were equally divided into an untreated group(vein grafts untreated),a gel group(vein grafts treated with gel only),an SCR group(vein grafts treated with gel containing scrambled siRNA) and a c-myc siRNA group(vein grafts treated with gel containing c-myc siRNA).The rats were sacrificed 3 weeks after surgery,and the grafted veins harvested for measurement of the intimal thickness under the microscope,determination of the expressions of the proliferating cell nuclear antigen(PCNA) and c-myc protein by immunohistochemistry,and detection of the content of c-myc mRNA by Q-RT-PCR.ResultsThe intimal thickness was(15.0±2.2) μm in the c-myc siRNA group,significantly less than in the untreated([58.3±8.3]μm),SCR([63.5±5.4]μm) and gel group([60.5±6.1]μm).The percentages of PCNA positive cells in the intima and media were significantly lower in the c-myc siRNA group([8.4±2.2]% and [15.0±3.1]%) than in the SCR group([68.5±5.0]% and [55.2±7.5]%)(P0.05),and so were the percentage of c-myc positive cells and the relative expression of c-myc mRNA in the c-myc siRNA than in the SCR group([30.6±2.6]% vs [48.5±3.5]% and 0.48±0.05 vs 1.00±0.12,P0.05).Conclusion Local administration of siRNA targeting c-myc can effectively inhibit the proliferation of vascular smooth muscle cells,suppress intimal hyperplasia,and thus ameliorate restenosis of the vein graft.