The Expression Of MTOR-P70S6K In Vascular Smooth Muscle Cells After Balloon Injury Of Rat Carotid Artery

Introduction:Restenosis is the major problem of atherosclerosis and percutaneous coronary interventions (PCI) due to the proliferation and migration of vascular smooth muscle. The aim of this study was to determine whether curcumin could suppress Interleukin-18 (IL-18), proliferating cell nuclear antigene (PCNA), mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinases (P70S6K) expression of vascular smooth muscle using balloon catheter-induced injury model in the rat carotid artery.Methods:Fifty four Sprague-Dawley rats were randomly divided into three groups, sham-operated rats, arterial injury rats, arterial injury rats treated with curcumin. The histological changes of vascular smooth muscle were observed dynamically, and vascular smooth muscle damage including vascular smooth muscle cell proliferation and interstitial fibrosis were quantified on HE tissue sections. The protein expression of PCNA and P70S6K were measured by immunohistochemistry. The mRNA expression of mTOR-P70S6K and PCNA were determined by real-time Quantitative PCR. Serum level of IL-18 was assessed by enzyme-linked immunosorbent assay (ELISA). Excel was used to build database, SPSS 11.0 was used for analyse.Results:The results showed that:Six rats were excluded from the experiment,one was dead during an operation of the experiment, another rats were found the artery occlusion (there was one rat died in the 3rd of drug intervention group and 7th injury groups, respectively; two rats were separately died in the 14th and 28th of drug intervention group). The remaining rats balloon injury model was successfully established.1 HE staining analysis:Media and intimal areas in treatment group at 14th day post-operation were larger than that in the 7th day (P=0.035 and <0.05, respectively). Media and intimal areas in treatment group decreased post-operation, while increased in sham-operated group. Both media and intimal areas were significantly different (P<0.05 respectively).2 The expression of P70S6K protein was increased after balloon-induced injury, The 7th and 14th injury group showed brown color, number of positive cells>70%; the 14th of drug intervention group pale yellow, number of positive cells<10%.; and there were significant differences between the study group and sham-operated group (P=0.045).3 The mRNA expression of mTOR-P70S6K and PCNA were not detectable in the sham-operated group, however, in study group, the expression of mTOR-P70S6K and PCNA were detected on the 3rd day after balloon-induced injury, reached the peak on the 14th day, and on the 28th day, strong expression of mTOR-P70S6K were observed.4 Strong immunoreactivity for IL-18 was detected in the serum level at 3 rd,7th and 14th after balloon injury. Moreover, serum concentrations of IL-18 were significantly higher among rats subjected to vascular injury.Conclusion:It was concluded that the alteration of mTOR-P70S6K and IL-18 might play an important role in aberrant proliferation within vascular remodeling following vascular injury. To block mTOR-P70S6K and IL-18 activation and the role of curcumin in arterial restenosis initiation may potentially provide a novel therapeutic medicine for the treatment and prevention of arterial restenosis.