Global gene expression profiling displays a network of dysregulated genes in non-atherosclerotic arterial tissue from patients with type 2 diabetes

To identify the molecular alterations of the generalized arterial disease in T2D, DNA microarrays were applied to examine gene expression changes in normal-appearing, non-atherosclerotic arterial tissue from 10 diabetic and 11 age-matched non-diabetic men scheduled for a coronary by-pass operation. Gene expression changes were integrated with GO-Elite, GSEA, and Cytoscape to identify significant biological pathways and networks.Global pathway analysis revealed differential expression of gene-sets representing matrix metabolism, triglyceride synthesis, inflammation, insulin signaling, and apoptosis. The network analysis showed a significant cluster of dysregulated genes coding for both intra- and extra-cellular proteins associated with vascular cell functions together with genes related to insulin signaling and matrix remodeling.Our results identify pathways and networks involved in the diffuse vasculopathy present in non-atherosclerotic arterial tissue in patients with T2D and confirmed previously observed mRNA-alterations. These abnormalities may play a role for the arterial response to injury and putatively for the accelerated atherogenesis among patients with diabetes.Cardiovascular diseases (CVD) in patients with type 2 diabetes are a large and increasing health problem. Increased atherosclerotic lesions are believed to form the basis behind the high frequency of CVD in diabetes; however, epidemiological studies have shown that traditional risk factors, e.g. hypertension and dyslipidemia cannot explain the increased incidence [1]. Unfortunately, the molecular mechanisms leading to atherosclerosis in diabetes are only partially understood [2].The arterial wall in diabetes harbors not only increased amounts of atherosclerotic plaques, but also diffuse alterations present in non-atherosclerotic parts of the vessel wall. One element of the generalized alterations in the vasculature in diabetes is endothelial dysfunction [3], characterized by increased permeability [