Effect Of Everolimus On The Neointimal Growth In Rats With Injured Carotid Artery By Balloon

Objective:To study the change of PCNA and eIF-4E in rat models with injured carotid artery by balloon and investigate the effect of oral everolimus on the neointimal growth, meanwhile, compare the effects of everolimus and it with statins-Rosuvastatin on restenosis, and analysis their possible mechanism.Methods:Forty healthy male SD rats were randomly divided into the sham-operated group (n=10), the injury group (injured carotid artery by balloon n=10), the everolimus group (injured carotid artery by balloon+oral everolimus n=10), and associated group (injured carotid artery by balloon+oral everolimus+oral rosuvastatin n=10). The sham operated group only carry on the operative procedure, not insert bollon injured. Everolimus 1.5 mg/kg was given 1 day before injured carotid artery by balloon, followed by 0.75 mg/kg per day for 28 days. and associated group, followed by fed with rosuvastatinn, The other groups were given with matching equivalent normal saline. Drugs were administered by oral gavage. Everolimus was given in the morning, and rosuvastatin was given in the evening. Carotid tissues of four groups were harvested 28 days after the injury, The target vascular sections were stained with HE to study the morphology changes. neointimal thickness, neointimal/media thickness, lumen area were measured by computer image analysis technique. and estimate the changes of vascular morphology. The expression of eukaryotic translation initiation factor 4E (eIF-4E) and proliferating cell nuclear antigen (PCNA) in arterial wall was detected by immunohistochemistry.Results:1. The injured group compared with sham-operated group:the neointima was formed and thickened distinctly, lumen stenosis distinctly (neointimal thickness 145.01±7.44 VS 1.23±0.13, lumen area 0.34±0.05 VS 0.85±0.03). the expression of eIF-4E and PCNA positive cells were significantly increased in the injury group, (eIF-4E positive ratio:93.3% VS 13.3%; PCNA positive cells:38.20±6.26 VS 0.98±0.94). Compared with the sham-operated group, No neointima was found. The expression of eIF-4E and PCNA positive cells were scarce (P<0.05).2. The everolimus group compared with the injured group, the neointimal area decreased (neointimal thickness 85.74±6.88 VS 145.01±7.44, lumen area 0.57±0.03 VS 0.34±0.05), the expression of eIF4E and PCNA decreased in the everolimus group (eIF-4E positive ratio:85.2% VS 93.3%; PCNA positive cells:16.56±1.97 VS 38.20±6.26) (P<0.05).3. The associated group compared with everolimus group, the neointimal area significantly reduced (neointimal thickness 44.11±7.05 VS 85.74±6.88, lumen area 0.78±0.02 VS 0.57±0.03), the expression of eIF4E and PCNA significantly reduced in the associated group (P<0.05).Conclusion:The neointimal grows distinctly in rats with injured carotid artery by balloon, the expression of eIF-4E and PCNA positive cells were significantly increased. Everrolimus can inhibit neointimal growth in rat models with injured carotid artery by balloon. So everrolimus could prevent restenosis, Treated with everrolimus and rosuvastatin are better than only everrolimus.