Oral rapamycin prevents artery restenosis after stent implantation by inhibiting mammalian target of rapamycin ( mTOR )

Abstract

Objective To identify the mechanisms of oral administered rapamycin on the prevention of restenosis after stent implantation with intravascular ultrasound (IVUS) and pathology.Methods Twenty-four New Zealand white rabbits underwent balloon-induced abdominal aortic wall injury and were given a diet of 1 ％ cholesterol for 8 weeks.Then,the rabbits were divided into three groups:the bare metal stent group(BMS group),the bare metal stent with oral rapamycin group(BMS + RAPA group) and the rapamycin eluting stent group(DES group).Rabbits in the RAPA and BMS + RAPA groups received a daily oral dose of rapamycin(0.5 mg/kg),whereas rabbits in the DES group received no drugs.All the rabbits were euthanized after the 4-week intervention.Serum lipids were measured.IVUS and pathologic studies were performed.The minimal luminal diameter (MLD),external elastic membrane (EEM) area,lumen area (LA),and plaque area(PA),plaque burden(PB) were measured.Mammalian target of rapamycin(mTOR) expression level was examined by immunohistochemistry.Results After the 4-week intervention,there was no significant difference of serum lipid levels among the three groups.IVUS showed that oral administration of rapamycin in the BMS + RAPA groups showed similar effects in reducing PA and PB as the DES group,which all were better than the BMS group.The BMS + RAPA and DES groups showed much more MLD and less lumen reduction,compared with the BMS group( P ＜0.05).Level of mTOR expression of the BMS + RAPA group and DES group was significantly lower than that of BMS group.Conclusions Oral administration of rapamycin demonstrates the same effect in the reduction of plaque burden and stent restenosis as the rapamycin eluting stent.Inhibition of mTOR by rapamycin involves in the stent restenosis. Key words: Endosonography; Atherosclerosis; Rapamycin; Stents; Restenosis