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Oral everolimus inhibits intimal proliferation in injured carotid artery in rats

Chinese Medical Journal 2013年第10期126卷 1906-1912页

作者： WANG Xiao-fang sHeN De-liang ZHAO Xiao-yan N1NG Hong-jie FeNG Ri-sheng ZHANG Jin-ying Department of Cardiology First Affiliated Hospital College ofMedicine Zhengzhou University Zhengzhou Henan 450052 China

Background everolimus, a derivative of sirolimus, is a potent immunosuppressant that has important anti-proliferative properties. In the present study, we demonstrated the inhibiting neointimal hyperplasia in injured carotid arteries in rats by using two different doses of everolimus administrated via the oral route for a long time. Methods A rat model of carotid artery injury was established by balloon inflation. eighty rats were randomly divided into the sham-operated group （n=20）, injury group （n=20）, low dosage of everolimus group （n=20）, and high dosage of everolimus group （n=20）. The low close of everolimus （1.5 mg/kg） was given one day before injuring the carotid artery by balloon, followed by 0.75 mg/kg per day for 28 days via intragastric gavage. High dose everolimus （2.5 mg/kg） was given one day before injuring the carotid artery by balloon, followed by 1 mg/kg per day for 28 days. expression of eukaryotic translation initiation factor 4e （elF-4e） and phosphorylation of ribosomal proteins6 kinase 1 （P70s6K） were determined by reverse transcription-polymerase chain reaction and Western blotting analysis. Results In the injured carotid artery, neointimal hyperplasia was normally observed four weeks after injury. everolimus inhibited neointimal hyperplasia after balloon injury in a dose dependent manner. At the same time, the study demonstrated that everolimus reduced the expression of P-P70s6K, elF-4e, transforming growth factor （TGF）-131 and of proliferating cell nuclear antigen （PCNA）. Conclusions everolimus significantly inhibited neointimal hyperplasia of the injured carotid artery. The effect depended on dosaqe and was associated with the reduction of phosphorylation of P70s6K and the elF-4e expression level.

关键词： everolimus ribosomal protein s6 kinase 1, eukaryotic translation initiation factor 4e

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