PDF(Pubmed)
Abstract：
Atherosclerosis differs across major arteries. Although the biological basis is not fully understood, limited evidence of genetic differences has been documented. This study, therefore, was aimed to identify differentially expressed genes between clinically relevant major arteries and investigate their enrichment in endothelial dysfunction-related gene sets. A bioinformatic analysis of publicly available gene-level read counts for coronary, aortic, and tibial arteries was performed. Differential gene expression was conducted with DeSeq2 at a false discovery rate of 0.05. Differentially expressed genes were then subjected to over-representation analysis and active-subnetwork-oriented enrichment analysis, both at a false discovery rate of 0.005. Enriched terms common to both analyses were categorized for each contrast into immunity/inflammation-, membrane biology-, lipid metabolism-, and coagulation-related terms, and the top differentially expressed genes validated against Swiss Institute of Bioinformatics\' Bgee database. There was mostly upregulation of differentially expressed genes for the coronary/tibial and aorta/tibial contrasts, but milder changes for the coronary/aorta contrast. Transcriptomic differences between coronary or aortic versus tibial samples largely involved immunity/inflammation-, membrane biology-, lipid metabolism-, and coagulation-related genes, suggesting potential to modulate endothelial dysfunction and atherosclerosis. These results imply atheroprone coronary and aortic environments compared with tibial artery tissue, which may explain observed relative inter-artery atherosclerosis risk.
摘要：
动脉粥样硬化在主要动脉中不同。虽然生物基础尚未完全了解，遗传差异的证据有限。这项研究,因此,旨在鉴定临床相关的主要动脉之间的差异表达基因，并研究它们在内皮功能障碍相关基因集中的富集。对公开的冠状动脉基因水平读数计数的生物信息学分析，主动脉,并进行了胫动脉检查。用DeSeq2以0.05的错误发现率进行差异基因表达。然后对差异表达的基因进行过表达分析和面向活性子网络的富集分析，两者的错误发现率为0.005。两种分析共有的丰富术语被分类为每个对比免疫/炎症-，膜生物学-，脂质代谢-，和凝血相关术语，以及在瑞士生物信息学研究所Bgee数据库中验证的最高差异表达基因。冠状动脉/胫骨和主动脉/胫骨对比的差异表达基因大多上调，但冠状动脉/主动脉造影的变化较温和。冠状动脉或主动脉与胫骨样本之间的转录组学差异主要涉及免疫/炎症-，膜生物学-，脂质代谢-，和凝血相关基因，提示调节内皮功能障碍和动脉粥样硬化的潜力。这些结果表明，与胫骨动脉组织相比，动脉粥样硬化的冠状动脉和主动脉环境，这可以解释观察到的相对动脉粥样硬化风险。
