Effect Of Everolimus Of Vascular Restenosis In Rats With Injured Carotid Artery By Balloon

Background Percutaneous transluminal coronary angioplasty(PTCA) has been an important method for treating coronary heart disease, but there are about thirty to fifty percent patients in the next 3-6 monthes after PTCA occuring restenosis. Though the the in-stent restenosis has descended to below ten percent by using the drug-eluting stent, the problem of DES in-stent restenosis are still being. The restenosis after PTCA is a process of neointimal proliferation and vascular remodeling. The proliferation of vascular smooth muscle cells aroused by endothelial injury plays a key role in in-stent restenosis. Therefore, it is very important to control the proliferation of vascular smooth muscle cells severely. It has been proved that rapamycin, a new immunosuppressor, could inhibit vascular smooth muscle cells proliferation and migration, and decrease in-stent restenosis. Everolimus, a derivative of rapamycin, is a new mammalian target of rapamycin inhibitor. It has an excellent function for inhibiting in-stent restenosis by using as surface coating in Xience V stent. Andrew Farb and his groups also proved that everolimus can inhibit neointimal proliferation in a model of New Zealand white rabbits with injured iliac arteries by balloon. Based on study above, we want to investigate the excellent effect of everolimus on vascular restenosis in rat models of carotid artery injury.Objective To investigate the effect of everolimus on vascular restenosis in rat models of carotid artery injury.Methods Thirty-six healthy male SD rats were randomly divided into three groups:control group, injury group and medicine group. Each group had 12 rats. The left common carotid arterys of the injury and medicine group were injured by balloon, and the external carotid arterys were ligated in the control cases. The medicine group rats were given everolimus 1.5mg/kg one day before operation by gavage, and followed by 0.75 mg/kg per day for 28 days. The rats in control group and injury group were gavaged with same amount of normal saline. All rats were killed at the 28th day and the left common carotid arterys of all animals were taken out. The vascular smooth muscle thickness and lumen area were measured after HE staining. The expression of p70s6k and transforming growth factor-β1 (TFG-β1) in arterial wall was detected by immunohistochemistry.ResultsThe vascular stenosis degree in medicine group was significantly lighter than injury group(vascular smooth muscle thickness,0.157±0.016mm vs 0.240±0.022mm, P<0.05; lumen area,1.015±0.045mm2 vs 0.746±0.050mm2, P<0.05). The expressions of p70s6k and TFG-β1 were not obvious in vascular smooth muscle cells of control group. The expressions of p70s6k and TFG-β1 in injury group and medicine group were significantly higher than control group(P<0.05), and the expressions in medicine group were lower than injury group(P<0.05).ConclusionEverrolimus could inhibit the proliferation of vascular smooth muscle cells in rats with injured carotid artery by balloon and reduce the rate of restenosis. The possible mechanism was in connection with inhibition the expression of p70s6k and TFG-β1.