Reduction of in-stent restenosis risk on nickel-free stainless steel by regulating cell apoptosis and cell cycle.

Reduction of in-stent restenosis risk on nickel-free stainless steel by regulating cell apoptosis and cell cycle.
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通过调节细胞凋亡和细胞周期降低无镍不锈钢支架内再狭窄风险

DOI:
10.1371/journal.pone.0062193
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Guan Y
Guan Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li L;Pan S;Zhou X;Meng X;Han X;Ren Y;Yang K;Guan Y

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高氮无镍奥氏体不锈钢(HNNF SS)是近年来发展起来的一种用于冠状动脉支架应用的生物材料。为了了解ISR抗性机制,我们对人脐静脉内皮细胞(HUVEC)对HNNF SS和316 L SS(含镍奥氏体316 L不锈钢)(目前使用的支架材料)的细胞和分子反应进行了比较研究。CCK-8分析和流式细胞术分析用于评估细胞反应(增殖、凋亡和细胞周期),并使用定量实时PCR(qRT-PCR)分析分别暴露于HNNF SS和316 L SS的HUVEC的基因表达谱。流式细胞仪分析表明,316 L SS比HNNF SS能更有效地激活细胞凋亡,并使细胞提前进入S期。在分子水平上,qRT-PCR结果显示调控细胞凋亡和自噬的基因在316 L SS上过表达。进一步的研究表明,316L SS释放的镍通过Fas-Caspase 8-Caspase 3外源性途径引发细胞凋亡。HUVEC的这些分子机制为阐明所观察到的细胞反应提供了良好的模型。本研究的发现为了解细胞和分子基础上的ISR抗性机制以及开发用于支架应用的新生物医学材料提供了有价值的信息。
High nitrogen nickel-free austenitic stainless steel (HNNF SS) is one of the biomaterials developed recently for circumventing the in-stent restenosis (ISR) in coronary stent applications. To understand the ISR-resistance mechanism, we have conducted a comparative study of cellular and molecular responses of human umbilical vein endothelial cells (HUVECs) to HNNF SS and 316L SS (nickel-containing austenitic 316L stainless steel) which is the stent material used currently. CCK-8 analysis and flow cytometric analysis were used to assess the cellular responses (proliferation, apoptosis, and cell cycle), and quantitative real-time PCR (qRT-PCR) was used to analyze the gene expression profile of HUVECs exposed to HNNF SS and 316L SS, respectively. Flow cytometry analysis revealed that 316L SS could activate the cellular apoptosis more efficiently and initiate an earlier entry into the S-phase of cell cycle than HNNF SS. At the molecular level, qRT-PCR results showed that the genes regulating cell apoptosis and autophagy were overexpressed on 316L SS. Further examination indicated that nickel released from 316L SS triggered the cell apoptosis via Fas-Caspase8-Caspase3 exogenous pathway. These molecular mechanisms of HUVECs present a good model for elucidating the observed cellular responses. The findings in this study furnish valuable information for understanding the mechanism of ISR-resistance on the cellular and molecular basis as well as for developing new biomedical materials for stent applications.
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