Systematically analyses of the common dysregulated networks to understand the common pathologies between T2D and atherosclerosis

Background: Diabetic macroangiopathy, atherosclerosis secondary to diabetes mellitus, causes cerebro-cardiovascular diseases (CVD), which increase the risk of death in patients with DM and significantly reduce their quality of life. Therefore, mechanisms underlying the common shared pathologies between type 2 diabetes (T2D) and atherosclerosis are key to prevention and treatment of diabetic macroangiopathy. However, the common shared pathological links between T2D and atherosclerosis are not fully understood.

Methods: We constructed a T2D and atherosclerosis associated protein interaction sub-network (TAN) to investigate common shared mechanisms between T2D and atherosclerosis. In addition, MCODE plugin of Cytoscape was applied to TAN to identify most significant functional modules. The network modules were further mapped to KEGG pathway enrichment analysis. Finally, we established a miRNA-gene regulatory network by searching disease associated miRNAs and integrated them into miRNA-gene interaction network for each module.

Results: TAN contains 1230 nodes which represent the union of T2D and atherosclerosis related genes and 3683 edges which represent the interactions of gene pairs. MCODE plugin was applied and five most significant modular clusters were identified. KEGG analysis of functional modules showed these genes were involved in several pathways including type 2 diabetes mellitus, ErbB and neurotrophin signaling pathway. miRNAgene interaction network was established and these miRNA-gene interactions mediated common shared pathologies between T2D and atherosclerosis.

Conclusions: Analysis of TAN demonstrated that modular organization of the interaction network elucidates shared pathologies of T2D and atherosclerosis. Furthermore, the disease associated miRNA-gene interaction network enriched our insight into role of miRNAs in mediating common shared pathologies between T2D and atherosclerosis. Thus, miRNAs constitute attractive targets for the development of novel therapies for treating both T2D and atherosclerosis.