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Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis

机译:基因表达的时程分析可确定支架内再狭窄患者中多个表达差异的基因

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Background The vascular disease in-stent restenosis (ISR) is characterized by formation of neointima and adverse inward remodeling of the artery after injury by coronary stent implantation. We hypothesized that the analysis of gene expression in peripheral blood mononuclear cells (PBMCs) would demonstrate differences in transcript expression between individuals who develop ISR and those who do not. Methods and Results We determined and investigated PBMC gene expression of 358 patients undergoing an index procedure to treat in de novo coronary artery lesions with bare metallic stents, using a novel time-varying intercept model to optimally assess the time course of gene expression across a time course of blood samples. Validation analyses were conducted in an independent sample of 97 patients with similar time-course blood sampling and gene expression data. We identified 47 probesets with differential expression, of which 36 were validated upon independent replication testing. The genes identified have varied functions, including some related to cellular growth and metabolism, such as the NAB2 and LAMP genes. Conclusions In a study of patients undergoing bare metallic stent implantation, we have identified and replicated differential gene expression in peripheral blood mononuclear cells, studied across a time series of blood samples. The genes identified suggest alterations in cellular growth and metabolism pathways, and these results provide the basis for further specific functional hypothesis generation and testing of the mechanisms of ISR.
机译:背景技术血管疾病支架内再狭窄(ISR)的特征在于新内膜的形成和冠状动脉支架植入术损伤后动脉的向内不良重构。我们假设,对外周血单个核细胞(PBMC)中基因表达的分析将证明发生ISR的人与未形成ISR的人在转录表达上的差异。方法和结果我们使用新颖的时变截距模型优化评估了一段时间内基因表达的时间进程,确定并调查了358例接受裸金属支架从头治疗冠脉病变的索引程序的PBMC基因表达。血样的过程。在97名患者的独立样本中进行了验证分析,这些样本具有类似的时程血样和基因表达数据。我们鉴定了47个差异表达的探针组,其中36个在独立复制测试中得到验证。鉴定出的基因具有多种功能,包括一些与细胞生长和代谢相关的功能,例如NAB2和LAMP基因。结论在一项对裸露的金属支架植入患者的研究中,我们已经鉴定并复制了在一系列血液样本中研究的外周血单核细胞中的差异基因表达。鉴定出的基因表明细胞生长和代谢途径发生了改变,这些结果为进一步特定功能假设的产生和ISR机理的测试提供了基础。

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