Significant difference between sirolimus and paclitaxel nanoparticles in antiproliferation effect in normoxia and hypoxia: The basis of better selection of atherosclerosis treatment  

作　　者：Youlu Chen Yong Zeng Xiaowei Zhu Lifu Miao Xiaoyu Liang Jianwei Duan Huiyang Li Xinxin Tian Liyun Pang Yongxiang Wei Jing Yang 

机构地区：[1]Tianjin Key Laboratory of Biomaterial Research,Institute of Biomedical Engineering,Chinese Academy of Medical Science and Peking Union Medical College,Tianjin,300192,PR China [2]Beijing Institute of Heart Lung and Blood Vessel Disease,Beijing Anzhen Hospital,Capital Medical University,Beijing,100029,PR China [3]Henan Center for Patent Examination and Cooperation of the Patent Office of the State Intellectual Property Office,Henan,450002,PR China [4]Heart Center,The First Hospital of Tsinghua University,Beijing,100016,PR China [5]Biomedical Barriers Research Center,Institute of Biomedical Engineering,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin,300192,PR China

出　　处：《Bioactive Materials》2021年第3期880-889,共10页生物活性材料（英文）

基　　金：support from the National Natural Science Foundation of China of China(31771097);Tianjin Research Program of Application Foundation and Advanced Technology(17JCZDJC3070);AMS Innovation Fund for Medical Sciences(2017-I2M-1–016);Tianjin Innovation and Promotion Plan Key Innovation Team of Immunoreactive Biomaterials.

摘　　要：Compared with paclitaxel,sirolimus has been more used in the treatment of vascular restenosis gradually as an anti-proliferative drug,but few basic studies have elucidated its mechanism.The anti-proliferative effects of sirolimus or paclitaxel have been demonstrated by numerous studies under normoxia,but few studies have been achieved focusing hypoxia.In this study,porcine carotid artery injury model and classical cobalt chloride hypoxia cell model were established.Sirolimus nanoparticles(SRM-NPs),paclitaxel nanoparticles(PTX-NPs)and blank nanoparticles(Blank-NPs)were prepared respectively.The effect of RPM-NPs on the degree of stenosis,proliferative index and the expression of PCNA after 28 days of porcine carotid artery injury model was evaluated.Compared with saline group and SRM groups,SRM-NPs group suppressed vascular stenosis,proliferative index and the expression of PCNA(P<0.01 and P<0.05).Endothelial cell(EC)and smooth muscle cell(SMC)were pre-treated with cobaltous chloride,followed by SRM-NPs,PTX-NPs,Blank-NPs or PBS control treating,the effects on cell proliferation,HIF-1 expression and glycolysis were detected.SRM-NPs could inhibit EC and SMC proliferation under hypoxia,while PTX-NPs couldn't(P<0.001).Significant differences between sirolimus and paclitaxel NPs in anti-proliferation effect under normoxia and hypoxia may due to the different inhibitory effects on HIF-1αexpression and glycolysis.In conclusion,these results suggest that sirolimus can inhibit the proliferation of hypoxic cells more effectively than paclitaxel.These observations may provide a basis for understanding clinical vascular stenosis therapeutic differences between rapamycin and paclitaxel.

关 键 词：ATHEROSCLEROSIS SIROLIMUS PACLITAXEL HYPOXIA HIF-1α Glycolysis 

分 类 号：R318[医药卫生—生物医学工程] TB383[医药卫生—基础医学]