title: Relationship of soluble RAGE and RAGE ligands HMGB1 and EN-RAGE to endothelial dysfunction in type 1 and type 2 diabetes mellitus.
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.
authors.affiliation: Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, U Nemocnice 1, Prague, Czech Republic. jan.skrha@seznam.cz
authors.forename: J
authors.initials: J
authors.lastname: Skrha
authors.forename: M
authors.initials: M
authors.lastname: Kalousová
authors.forename: J
authors.initials: J
authors.lastname: Svarcová
authors.forename: A
authors.initials: A
authors.lastname: Muravská
authors.forename: J
authors.initials: J
authors.lastname: Kvasnička
authors.forename: L
authors.initials: L
authors.lastname: Landová
authors.forename: T
authors.initials: T
authors.lastname: Zima
authors.forename: J
authors.initials: J
authors.lastname: Skrha
mesh_terms: D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D045726:Metalloproteases / Q000097:blood; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D045726:Metalloproteases; D020780:Matrix Metalloproteinase 9