Butt H Z, Sylvius N, Salem M K, Wild J B, Dattani N, Sayers R D, Bown M J
Vascular Surgery Group, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Vascular Surgery Group, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Eur J Vasc Endovasc Surg. 2016 Jul;52(1):47-55. doi: 10.1016/j.ejvs.2016.03.016. Epub 2016 May 3.
OBJECTIVE/BACKGROUND: Microarray-based gene expression profiling studies may detect transcriptional signatures carrying prognostic value in abdominal aortic aneurysms (AAA). A gene expression profiling study was conducted to compare individuals with AAA with screened controls.
The peripheral blood transcriptome was compared between 12 individuals with AAA and 12 age- and sex-matched controls using microarray. Validation by Taqman real-time quantitative (qPCR) was performed in an independent group as described. Peripheral blood RNA was hybridized to Illumina microarrays, each representing 37,846 genes, allowing comparison of gene expression between cases and controls. Eleven differentially expressed genes were re-quantified by qPCR in the independent group with AAA (n = 95), controls (n = 92), pre- and postendovascular AAA repair (EVAR, n = 31); or open AAA repair (n = 13), AAA wall biopsies (n = 11), and in matched smooth muscle cultures (n = 7).
Microarray detected 47 significantly differentially expressed genes in AAA after correction for multiple testing (p < .05). These genes conferred roles in regulation of apoptosis, proteolysis, the electron transport chain, leukocyte migration, and the humoral immune response. Gene quantification in the independent group demonstrated three genes to be downregulated in AAA compared with controls: MSN, PSMB10, and STIM1; however, their expression remained unchanged post-AAA repair. PSMB10 was the only gene conferring a consistent direction of effect in both the discovery and validation analyses (downregulated). EIF3G, SIVA, PUF60, CYC1, FIBP, and CARD8 were downregulated post-EVAR. Expression of all 11 genes of interest was detected in aortic biopsies and matched smooth muscle cultures.
This study demonstrates differential expression of transcripts in peripheral blood of individuals with AAA, with functional roles in proteolysis, inflammation, and apoptotic processes. These were modulated by aneurysm exclusion from the circulation and expressed in matched aortic biopsies and smooth muscle cultures. These observations further support the key roles for these pathways in the pathogenesis of AAA.
目的/背景：基于微阵列的基因表达谱研究可能检测到携带腹主动脉瘤（AAA）预后价值的转录特征。开展了一项基因表达谱研究，以比较AAA患者与筛查对照。
使用微阵列比较了12例AAA患者和12例年龄及性别匹配的对照的外周血转录组。如所述，在一个独立队列中通过Taqman实时定量（qPCR）进行验证。外周血RNA与Illumina微阵列杂交，每个微阵列代表37,846个基因，从而能够比较病例组和对照组之间的基因表达。在独立的AAA队列（n = 95）、对照组（n = 92）、血管内AAA修复术前和术后（EVAR，n = 31）；或开放性AAA修复（n = 13）、AAA壁活检（n = 11）以及匹配的平滑肌培养物（n = 7）中，通过qPCR对11个差异表达基因进行重新定量。
经过多重检验校正后，微阵列检测到AAA中有47个显著差异表达基因（p <.05）。这些基因在细胞凋亡调节、蛋白水解、电子传递链、白细胞迁移和体液免疫反应中发挥作用。独立队列中的基因定量显示，与对照组相比，AAA中有三个基因下调：MSN、PSMB10和STIM1；然而，它们在AAA修复后的表达保持不变。PSMB10是在发现和验证分析中唯一具有一致效应方向（下调）的基因。EIF3G、SIVA、PUF60、CYC1、FIBP和CARD8在EVAR术后下调。在主动脉活检和匹配的平滑肌培养物中检测到了所有11个感兴趣基因的表达。
本研究证明了AAA患者外周血中转录本的差异表达，这些转录本在蛋白水解、炎症和凋亡过程中发挥功能作用。它们受到动脉瘤从循环中排除的调节，并在匹配的主动脉活检和平滑肌培养物中表达。这些观察结果进一步支持了这些途径在AAA发病机制中的关键作用。
