Stather Philip W, Sylvius Nicolas, Wild John B, Choke Edward, Sayers Robert D, Bown Matthew J
Department of Cardiovascular Sciences and Department of Genetics and the NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
Circ Cardiovasc Genet. 2013 Oct;6(5):490-7. doi: 10.1161/circgenetics.111.000053.
Peripheral arterial disease (PAD) is a clinical condition caused by an atherosclerotic process affecting the arteries of the limbs. Despite major improvements in surgical endovascular techniques, PAD is still associated with high mortality and morbidity. Recently, microRNAs (miRNAs), a class of short noncoding RNA controlling gene expression, have emerged as major regulators of multiple biological processes.
A whole-miRNA transcriptome profiling was performed in peripheral blood from an initial sample set of patients and controls. A 12-miRNA PAD-specific signature, which includes let 7e, miR-15b, -16, -20b, -25, -26b, -27b, -28-5p, -126, -195, -335, and -363, was further investigated and validated in 2 additional sample sets. Each of these 12 miRNAs exhibited good diagnostic value as evidenced by receiver operating characteristic curve analyses. Pathway enrichment analysis using predicted and validated targets identified several signaling pathways relevant to vascular disorders. Several of these pathways, including cell adhesion molecules, were confirmed by quantifying the expression level of several candidate genes regulating the initial stages of the inflammatory atherosclerotic process. The expression level of 7 of these candidate genes exhibits striking inverse correlation with that of several, if not all, of the miRNAs of the PAD-specific miRNA signature.
These results demonstrate the potential of miRNAs for the diagnosis of PAD and provide further insight into the molecular mechanisms leading to the development of PAD, with the potential for future therapeutic targets.
外周动脉疾病（PAD）是一种由影响肢体动脉的动脉粥样硬化过程引起的临床病症。尽管外科血管内技术有了重大改进，但PAD仍然与高死亡率和高发病率相关。最近，微小RNA（miRNA），一类控制基因表达的短非编码RNA，已成为多种生物学过程的主要调节因子。
对患者和对照的初始样本集的外周血进行了全miRNA转录组分析。进一步研究并在另外2个样本集中验证了一个由12种miRNA组成的PAD特异性特征，其中包括let-7e、miR-15b、-16、-20b、-25、-26b、-27b、-28-5p、-126、-195、-335和-363。这些12种miRNA中的每一种都表现出良好的诊断价值，这在受试者工作特征曲线分析中得到了证实。使用预测和验证的靶标进行的通路富集分析确定了几个与血管疾病相关的信号通路。通过量化几个调节炎症性动脉粥样硬化过程初始阶段的候选基因的表达水平，证实了其中几个通路，包括细胞粘附分子。这些候选基因中的7个的表达水平与PAD特异性miRNA特征中的几种（如果不是全部）miRNA的表达水平呈现出显著的负相关。
这些结果证明了miRNA在诊断PAD方面的潜力，并进一步深入了解了导致PAD发生发展的分子机制，具有未来治疗靶点的潜力。
