Department of Visceral, Thoracic and Vascular Surgery, Technical University of Dresden, Dresden, Germany.
Pathobiology. 2013;80(1):1-10. doi: 10.1159/000339303. Epub 2012 Jul 12.
Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs.
A custom-designed 'AAA-chip' was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta. Protein analyses were performed on selected genes.
Altogether 38 of the 43 genes on the 'AAA-chip' showed significantly different expression. Novel validated genes in AAA pathobiology included ADCY7, ARL4C, BLNK, FOSB, GATM, LYZ, MFGE8, PRUNE2, PTPRC, SMTN, TMODI and TPM2. These genes represent a wide range of biological functions, such as calcium signaling, development and differentiation, as well as cell adhesion not previously implicated in AAA pathobiology. Protein analyses for GATM, CD4, CXCR4, BLNK, PLEK, LYZ, FOSB, DUSP6, ITGA5 and PTPRC confirmed the mRNA findings.
The results provide new directions for future research into AAA pathogenesis to study the role of novel genes confirmed here. New treatments and diagnostic tools for AAA could potentially be identified by studying these novel pathways.
腹主动脉瘤(AAA)是肾下主动脉的扩张,通常影响 65 岁以上的男性。人类 AAA 的病理生物学机制尚不清楚。本研究的目的是确定参与 AAA 发展的新途径。
使用定制的“AAA 芯片”来检测先前发表的微阵列研究中 AAA(n = 15)和对照(n = 15)肾下腹部主动脉之间差异表达的 43 个基因中的 43 个。对选定的基因进行蛋白质分析。
总共 43 个“AAA 芯片”上的基因显示出明显不同的表达。AAA 病理生物学中的新验证基因包括 ADCY7、ARL4C、BLNK、FOSB、GATM、LYZ、MFGE8、PRUNE2、PTPRC、SMTN、TMODI 和 TPM2。这些基因代表了广泛的生物学功能,如钙信号转导、发育和分化,以及以前与 AAA 病理生物学无关的细胞粘附。GATM、CD4、CXCR4、BLNK、PLEK、LYZ、FOSB、DUSP6、ITGA5 和 PTPRC 的蛋白质分析证实了 mRNA 结果。
这些结果为 AAA 发病机制的未来研究提供了新的方向,以研究这里证实的新基因的作用。通过研究这些新途径,可能会发现新的 AAA 治疗和诊断工具。