The Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
School of Nursing and Midwifery, University of Newcastle, Callaghan, NSW, Australia.
Sci Rep. 2017 Jun 28;7(1):4338. doi: 10.1038/s41598-017-04497-9.
The aim of this study was to identify genes for which the expression within carotid atherosclerosis was reproducibly associated with the symptoms of cerebral embolization. Two publically available microarray datasets E-MEXP-2257 and GSE21545 were analysed using GeneSpring 11.5. The two datasets utilized a total of 22 and 126 carotid atherosclerosis samples, obtained from patients with and without symptoms of cerebral embolization, respectively. To assess whether the findings were reproducible we analysed carotid atherosclerosis samples from another 8 patients with and 7 patients without symptoms of cerebral embolization using real-time PCR. In vitro studies using VSMC were performed to assess the functional relevance of one of the validated genes. We identified 1624 and 135 differentially expressed genes within carotid atherosclerosis samples of symptomatic compared to asymptomatic patients using the E-MEXP-2257 and GSE21545 datasets, respectively (≥1.15-absolute fold-change, P < 0.05). Only 7 differentially expressed genes or 0.4% (7/1,752) were consistent between the datasets. We validated the differential expression of ARSB which was upregulated 1.15-fold (P = 0.029) in atherosclerosis from symptomatic patients. In vitro incubation of VSMCs with the ARSB inhibitor L-ascorbic acid resulted in marked upregulation of SIRT1 and AMPK. This study suggests that ARSB may represent a novel target to limit carotid embolization.
本研究旨在鉴定在颈动脉粥样硬化中表达与脑栓塞症状有重复相关性的基因。使用 GeneSpring 11.5 分析了两个公开的微阵列数据集 E-MEXP-2257 和 GSE21545。这两个数据集共利用了 22 个和 126 个颈动脉粥样硬化样本，分别来自有和没有脑栓塞症状的患者。为了评估发现是否可重现，我们使用实时 PCR 分析了另外 8 名有和 7 名无症状脑栓塞患者的颈动脉粥样硬化样本。使用 VSMC 进行体外研究，以评估验证的基因之一的功能相关性。使用 E-MEXP-2257 和 GSE21545 数据集，我们分别鉴定出颈动脉粥样硬化样本中与无症状患者相比有症状患者中 1624 个和 135 个差异表达基因（≥1.15-绝对倍数变化，P<0.05）。两个数据集之间仅 7 个差异表达基因或 0.4%（7/1752）一致。我们验证了 ARSB 的差异表达，其在有症状患者的动脉粥样硬化中上调了 1.15 倍（P=0.029）。体外孵育 VSMC 与 ARSB 抑制剂 L-抗坏血酸导致 SIRT1 和 AMPK 的显著上调。这项研究表明，ARSB 可能代表限制颈动脉栓塞的一个新靶标。
