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

Cardiovasc Diabetol. 2012 Feb 17;11:15. doi: 10.1186/1475-2840-11-15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Arteries / metabolism*
  • Arteries / pathology
  • Biopsy
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Gene Expression Profiling*
  • Genes / genetics*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Insulin / metabolism
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Triglycerides / metabolism

Substances

  • Insulin
  • Triglycerides

Associated data

  • GEO/GSE13760