Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
Exp Biol Med (Maywood). 2021 Dec;246(23):2487-2494. doi: 10.1177/15353702211033247. Epub 2021 Jul 25.
Atherosclerotic plaque destabilization is a dominating cause of acute cardiovascular events such as myocardial infarction and stroke. This study aims to identify genetic biomarkers related to atherosclerotic plaque destabilization using bioinformatics. Three transcriptome datasets of human carotid atherosclerotic plaque samples were downloaded from ArrayExpress and Gene Expression Omnibus databases, including E-MATB-2055, E-TABM-190, and GSE120521. With Robust Rank Aggregation analysis, we documented 46 differentially expressed genes between stable and unstable/ruptured plaques. Functional enrichment analysis using DAVID tool demonstrated that these genes were mainly related to biological functions such as extracellular matrix disassembly, collagen catabolic process, response to mechanical stimulus, and PPAR signaling pathway. A protein-protein interaction network for the differentially expressed genes was constructed, and eight pivotal genes (, , , , , , , and ) were obtained from the network with a connective degree > 5. The expression patterns of these hub differentially expressed genes could be verified in atherosclerotic plaque samples with intraplaque hemorrhage. Using gene set variation analysis, the eight genes were integrated to generate an atherosclerotic plaque destabilization score, which showed a high performance in not only discriminating individuals with myocardial infarction from those with stable coronary illness, but also in predicting future acute cardiovascular events in atherosclerotic patients. In conclusion, the findings of this study will enhance our knowledge on the pathological mechanisms involved in atherosclerotic plaque destabilization, and provide potential gene biomarkers for risk stratification of patients with atherosclerotic cardiovascular disease.
动脉粥样硬化斑块不稳定是急性心血管事件（如心肌梗死和中风）的主要原因。本研究旨在使用生物信息学方法鉴定与动脉粥样硬化斑块不稳定相关的遗传生物标志物。从 ArrayExpress 和 Gene Expression Omnibus 数据库中下载了三个人类颈动脉粥样硬化斑块样本的转录组数据集，包括 E-MATB-2055、E-TABM-190 和 GSE120521。通过稳健秩聚合分析，我们记录了稳定斑块和不稳定/破裂斑块之间的 46 个差异表达基因。使用 DAVID 工具进行的功能富集分析表明，这些基因主要与生物学功能有关，如细胞外基质解体、胶原分解代谢过程、对机械刺激的反应和 PPAR 信号通路。构建了差异表达基因的蛋白质-蛋白质相互作用网络，从网络中获得了 8 个关键基因（、、、、、、和），其连接度>5。这些关键差异表达基因的表达模式可以在有斑块内出血的动脉粥样硬化斑块样本中得到验证。通过基因集变异分析，将这 8 个基因整合在一起，生成了一个动脉粥样硬化斑块不稳定评分，该评分不仅能区分心肌梗死患者和稳定型冠心病患者，而且能预测动脉粥样硬化患者未来的急性心血管事件。总之，本研究的结果将增强我们对动脉粥样硬化斑块不稳定相关病理机制的认识，并为动脉粥样硬化性心血管疾病患者的风险分层提供潜在的基因生物标志物。
