Relationship of soluble RAGE and RAGE ligands HMGB1 and EN-RAGE to endothelial dysfunction in type 1 and type 2 diabetes mellitus

Exp Clin Endocrinol Diabetes. 2012 May;120(5):277-81. doi: 10.1055/s-0031-1283161. Epub 2012 Apr 27.

Abstract

Receptor for advanced glycation end-products (RAGE) plays the essential role in the pathogenesis of diabetic vascular complications. The aim of the study was to compare concentration of soluble RAGE and its ligands (EN-RAGE and HMGB1) with different biochemical parameters in Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus.Total number of 154 persons (45 T1DM, 68 T2DM, 41 controls) was examined and concentrations of sRAGE, EN-RAGE and HMGB1 were measured and compared to diabetes control, albuminuria, cell adhesion molecules and metalloproteinases (MMPs).Mean serum sRAGE concentration was higher in T1DM as compared to controls (1137±532 ng/l vs. 824±309 ng/l, p<0.01). Similarly, EN-RAGE was significantly higher in both diabetic groups (p<0.001) and HMGB1 concentrations were elevated in T2DM patients (p<0.01). Significant relationship was found between MMP9 and HMGB1 and EN-RAGE in diabetic patients. Inverse relationship was observed between MMP2 and MMP9 in both types of diabetic patients (r= - 0.602, p<0.002 and r= - 0.771, p<0.001). Significant positive correlation was found between sRAGE and ICAM-1, VCAM-1 or vWF (p<0.01 to p<0.001).We conclude that serum sRAGE and RAGE ligands concentrations reflect endothelial dysfunction developing in diabetes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Adhesion Molecules / blood
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / pathology
  • Endothelium, Vascular / pathology*
  • Female
  • HMGB1 Protein / blood*
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / blood
  • Metalloproteases / blood
  • Middle Aged
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / blood*
  • S100 Proteins / blood*
  • S100A12 Protein
  • Statistics, Nonparametric
  • Young Adult

Substances

  • Cell Adhesion Molecules
  • HMGB1 Protein
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • S100 Proteins
  • S100A12 Protein
  • S100A12 protein, human
  • Metalloproteases
  • Matrix Metalloproteinase 9