Pan Sun, Wu Duojiao, Teschendorff Andrew E, Hong Tao, Wang Linyan, Qian Mengjia, Wang Chunsheng, Wang Xiangdong
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, China.
PLoS One. 2014 Feb 24;9(2):e89406. doi: 10.1371/journal.pone.0089406. eCollection 2014.
The precise mechanisms underlying dissections, especially those without connective tissue diseases or congenital vascular diseases, are incompletely understood. This study attempted to identify both the expression profile of the dissected ascending aorta and the interactome hotspots associated with the disease, using microarray technology and gene regulatory network analysis. There were 2,737 genes differentially expressed between patients with acute Stanford type A aortic dissection and controls. Eight interactome hotspots significantly associated with aortic dissection were identified by an integrative network algorithm. In particular, we identified a JAK2-centered expression module, which was validated in an independent gene expression microarray data set, and which was characterized by over-expressed cytokines and receptors in acute aortic dissection cases, indicating that JAK2 may play a key role in the inflammatory process, which potentially contributes to the occurrence of acute aortic dissection. Overall, the analytical strategy used in this study offered the possibility to identify functional relevant network modules and subsequently facilitated the biological interpretation in the complicated disease.
夹层形成的精确机制，尤其是那些没有结缔组织疾病或先天性血管疾病的夹层形成机制，目前尚未完全明确。本研究试图利用微阵列技术和基因调控网络分析，确定夹层升主动脉的表达谱以及与该疾病相关的相互作用组热点。急性A型主动脉夹层患者与对照组之间有2737个基因差异表达。通过整合网络算法确定了8个与主动脉夹层显著相关的相互作用组热点。特别是，我们确定了一个以JAK2为中心的表达模块，该模块在一个独立的基因表达微阵列数据集中得到验证，其特征是急性主动脉夹层病例中细胞因子和受体过度表达，这表明JAK2可能在炎症过程中起关键作用，而炎症过程可能促成急性主动脉夹层的发生。总体而言，本研究中使用的分析策略为识别功能相关的网络模块提供了可能性，并随后促进了对复杂疾病的生物学解释。
