Relationship of Soluble RAGE and RAGE Ligands HMGB1 and EN-RAGE to Endothelial Dysfunction in Type 1 and Type 2 Diabetes Mellitus

Aims: 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. Methods: 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). Results: 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). Conclusion: We conclude that serum sRAGE and RAGE ligands concentrations reflect endothelial dysfunction developing in diabetes.