The most common approach to genomic analysis starts with the identification of differentially expressed genes and subsequent biological interpretation using Gene Set Enrichment Analysis. According to our definition, Limma analysis of the microarray data identified 2737 differentially expressed genes between 7 GDC-0879 905281-76-7 aortic dissection cases and 5 controls. Of the top 25 differentially expressed genes, 17 genes were up-regulated and 8 were downregulated in cases. However, the common approach may miss important biological pathways, because the inference does not take the pathway or network structure into account and because changes affecting individual features are often of a small magnitude. Thus, a number of statistical approaches have emerged using the pathway/network structure in the inference procedure. Here we used a novel integrative approach to infer network modules, which subsequently facilitated the biological interpretation. By this integrative network algorithm, interactome hotspots associated with aortic dissection were identified. Among them, we found a JAK2 module, which was validated in an independent gene expression microarray data set, enriched for cytokines and receptors, including IL-6, IL-6R, CCL2 and IFNGR2. That many cytokines are implicated in AAD is well supported by previous literature: for instance, IL-6, INF gamma and CCL2, were observed to be significantly increased in AAD patients. The previous microarray study also observed that IL-2, -6 and -8 genes were up-regulated in aortic dissection. It has also been noted that IL-6 is secreted at high levels in human aortic aneurysm disease. These data indicate an inflammatory process characterized by abnormal expression of cytokines in aortic disease. Vascular inflammation is a common pathologic and physiological response in diverse cardiovascular disease processes, including atherosclerosis, myocardial infarction and congestive heart failure. Furthermore, IL-6 is found to be linked with the development of coronary disease and atherosclerosis. Taking all the factors together, it is reasonable to hypothesize that chronic inflammation may probably play a contributory role in the pathogenesis of aortic dissection. However, the precise relationship between inflammation and AAD remains complicated and the specific pattern of the inflammation as well as the key regulators is still pending. Therefore, when JAK2, one of the top 25 genes from Limma analysis, came up also as the hotspot, it was of particular interest to further discuss its potential biological significance. The JAK family plays a critical role in growth, development, survival and differentiation through signal transduction of many cytokine receptors. STAT3, a downstream transducer activated by JAKs, was found to be involved in vascular abnormalities. Frequent cerebral and coronary artery ectasias and aneurysms were observed in patients with STAT3 deficiency.