PADPIN: protein-protein interaction networks of angiogenesis, arteriogenesis, and inflammation in peripheral arterial disease
PADPIN: protein-protein interaction networks of angiogenesis, arteriogenesis, and inflammation in peripheral arterial disease
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DOI：
10.1152/physiolgenomics.00125.2014
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发表时间：
2015-08-01
影响因子：
4.6
通讯作者：
Popel, Aleksander S.
中科院分区：
文献类型：
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作者：
Chu, Liang-Hui;Vijay, Chaitanya G.;Popel, Aleksander S.
外周动脉疾病（PAD）是由心脏以外的动脉（最常见的是供应腿部的动脉）中的血流阻塞引起的。PAD中涉及的已知信号传导途径的复杂性，包括各种生长因子途径及其相互作用，表明对高通量实验数据的分析可能会导致对该疾病以及新的和迄今为止未预料到的潜在靶点的新水平的理解。尚未对PAD进行系统的生物信息学分析。我们使用我们先前开发的算法GeneHits构建了血管生成（Angiome），免疫反应（Immunome）和动脉生成（Arteriome）的全球蛋白质-蛋白质相互作用网络。术语“PADPIN”是指PAD中的血管组、免疫组和动脉组。在这里，我们分析了四个微阵列基因表达数据集缺血和非缺血腓肠肌在后肢缺血（HLI）后3天在两个遗传上不同的C57 BL/6和BALB/c小鼠品系，显示差异易感性HLI，以确定潜在的目标和信号通路的血管生成，免疫和动脉生成网络。我们假设，缺血和非缺血性肌肉之间的差异表达基因的菌株，恢复更好（C57 BL/6）与恢复更差（BALB/c）的菌株之间的鉴定将有助于预测PAD的靶基因。我们的生物信息学分析鉴定了在PAD中具有已知功能的两种小鼠品系之间差异表达的几个基因，包括TLR 4、THBS 1和PRKAA 2，以及在PAD中具有未知功能的几个基因，包括EphA 4、TSPAN 7、SLC 22 A4和EIF 2a。
Peripheral arterial disease (PAD) results from an obstruction of blood flow in the arteries other than the heart, most commonly the arteries that supply the legs. The complexity of the known signaling pathways involved in PAD, including various growth factor pathways and their cross talks, suggests that analyses of high-throughput experimental data could lead to a new level of understanding of the disease as well as novel and heretofore unanticipated potential targets. Such bioinformatic analyses have not been systematically performed for PAD. We constructed global protein-protein interaction networks of angiogenesis (Angiome), immune response (Immunome), and arteriogenesis (Arteriome) using our previously developed algorithm GeneHits. The term "PADPIN" refers to the angiome, immunome, and arteriome in PAD. Here we analyze four microarray gene expression datasets from ischemic and nonischemic gastrocnemius muscles at day 3 post-hindlimb ischemia (HLI) in two genetically different C57BL/6 and BALB/c mouse strains that display differential susceptibility to HLI to identify potential targets and signaling pathways in angiogenesis, immune, and arteriogenesis networks. We hypothesize that identification of the differentially expressed genes in ischemic and nonischemic muscles between the strains that recovers better (C57BL/6) vs. the strain that recovers more poorly (BALB/c) will help for the prediction of target genes in PAD. Our bioinformatics analysis identified several genes that are differentially expressed between the two mouse strains with known functions in PAD including TLR4, THBS1, and PRKAA2 and several genes with unknown functions in PAD including EphA4, TSPAN7, SLC22A4, and EIF2a.