title: Reduction of in-stent restenosis risk on nickel-free stainless steel by regulating cell apoptosis and cell cycle.
abstract: 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.
authors: Key Laboratory of Medical Cell Biology, Ministry of Education, Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China.
authors: Liming
authors: L
authors: Li
authors: Shuang
authors: S
authors: Pan
authors: Xiaohang
authors: X
authors: Zhou
authors: Xin
authors: X
authors: Meng
authors: Xiaoxi
authors: X
authors: Han
authors: Yibin
authors: Y
authors: Ren
authors: Ke
authors: K
authors: Yang
authors: Yifu
authors: Y
authors: Guan
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D023903:Coronary Restenosis / Q000209:etiology* / Q000517:prevention & control*; D005434:Flow Cytometry; D005453:Fluorescence; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009532:Nickel / Q000494:pharmacology*; D061848:Optical Imaging; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013193:Stainless Steel / Q000494:pharmacology*; D015607:Stents / Q000009:adverse effects*
chemical_list: C426023:austenitic steel; D013193:Stainless Steel; D009532:Nickel
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