Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Genes (Basel). 2021 Mar 9;12(3):387. doi: 10.3390/genes12030387.
Acute aortic dissection is one of the most severe vascular diseases. The molecular mechanisms of aortic expansion and dissection are unclear. Clinical studies have found that statins play a protective role in aortic dissection development and therapy; however, the mechanism of statins' effects on the aorta is unknown. The Gene Expression Omnibus (GEO) dataset GSE52093, GSE2450and GSE8686 were analyzed, and genes expressed differentially between aortic dissection samples and normal samples were determined using the Networkanalyst and iDEP tools. Weight gene correlation network analysis (WGCNA), functional annotation, pathway enrichment analysis, and the analysis of the regional variations of genomic features were then performed. We found that the minichromosome maintenance proteins (MCMs), a family of proteins targeted by statins, were upregulated in dissected aortic wall tissues and play a central role in cell-cycle and mitosis regulation in aortic dissection patients. Our results indicate a potential molecular target and mechanism for statins' effects in patients with acute type A aortic dissection.
急性主动脉夹层是最严重的血管疾病之一。主动脉扩张和夹层的分子机制尚不清楚。临床研究发现，他汀类药物在主动脉夹层的发生和治疗中起保护作用；然而，他汀类药物对主动脉的作用机制尚不清楚。本研究分析了基因表达综合数据库（GEO）数据集 GSE52093、GSE2450 和 GSE8686，使用 Networkanalyst 和 iDEP 工具确定了主动脉夹层样本和正常样本之间差异表达的基因。然后进行加权基因共相关网络分析（WGCNA）、功能注释、通路富集分析以及基因组特征区域变异分析。我们发现，他汀类药物的作用靶点——微小染色体维持蛋白（MCMs）家族在夹层主动脉壁组织中上调，在主动脉夹层患者的细胞周期和有丝分裂调控中起核心作用。我们的研究结果表明，他汀类药物在急性 A 型主动脉夹层患者中的作用存在潜在的分子靶点和机制。
