title: Global gene expression profiling displays a network of dysregulated genes in non-atherosclerotic arterial tissue from patients with type 2 diabetes.
abstract: BACKGROUND
  Generalized arterial alterations, such as endothelial dysfunction, medial matrix accumulations, and calcifications are associated with type 2 diabetes (T2D). These changes may render the vessel wall more susceptible to injury; however, the molecular characteristics of such diffuse pre-atherosclerotic changes in diabetes are only superficially known.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark. vibe.skov@ouh.regionsyddanmark.dk
authors.forename: Vibe
authors.initials: V
authors.lastname: Skov
authors.forename: Steen
authors.initials: S
authors.lastname: Knudsen
authors.forename: Malene
authors.initials: M
authors.lastname: Olesen
authors.forename: Maria L
authors.initials: ML
authors.lastname: Hansen
authors.forename: Lars M
authors.initials: LM
authors.lastname: Rasmussen
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001158:Arteries / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005796:Genes / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
chemical_list: D007328:Insulin; D014280:Triglycerides