title: Endothelial cell adhesion molecule and PMNL response to inflammatory stimuli and AGE-modified fibronectin.
abstract: BACKGROUND
  Atherosclerotic vascular disease is the leading cause of death in patients with diabetes mellitus and end-stage renal disease. Advanced glycation end products (AGEs) are strongly suggested to be involved in the pathogenesis of atherosclerosis in these patients who also frequently experience infectious complications. We hypothesized that the interaction of AGEs and inflammatory mediators contributes to the up-regulation of endothelial cell activation.
  
  
  METHODS
  We investigated the effect of advanced glycated fibronectin in the presence or absence of inflammatory stimuli on the endothelial cell surface and mRNA expression of cell adhesion molecules. Furthermore, the influence of advanced glycated fibronectin on the transendothelial migration pattern of polymorphonuclear cells was analyzed.
  
  
  RESULTS
  Exposure to advanced glycated fibronectin together with inflammatory stimuli such as interleukin (IL)-1alpha, tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) led to a significant increase in the surface expression of the cell adhesion molecules E-selectin, ICAM-1, VCAM-1 and PECAM-1 on endothelial cells. Soluble AGEs in combination with advanced glycated fibronectin significantly enhanced the endothelial cell surface expression of ICAM-1, VCAM-1 and PECAM-1, whereas this was not the case for E-selectin. At the transcriptional level short-time exposure of endothelial cells to advanced glycated fibronectin and inflammatory mediators resulted in an increased expression of E-selectin, ICAM-1 and VCAM-1 mRNA levels, whereas PECAM-1 repeatedly showed a significant decrease of gene transcript levels. An increase of mRNA levels was also observed for E-selectin, ICAM-1, VCAM-1 and PECAM-1 following incubation with a combination of advanced glycated fibronectin and soluble advanced glycation end-products. Furthermore, polymorphonuclear cells responded with a sevenfold increase in transendothelial migration following exposure of endothelial cells to advanced glycated fibronectin and inflammatory mediators.
  
  
  CONCLUSIONS
  These results suggest that the combination of matrix glycation and inflammation up-regulates the activation of the endothelial cell adhesion cascade, a mechanism that might contribute to the increased burden of atherosclerotic morbidity and mortality in patients suffering from diabetes mellitus or chronic renal failure.
authors.affiliation: Department of Internal Medicine III, Division of Nephrology, University of Vienna, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Sengoelge
authors.forename: M
authors.initials: M
authors.lastname: Födinger
authors.forename: S
authors.initials: S
authors.lastname: Skoupy
authors.forename: I
authors.initials: I
authors.lastname: Ferrara
authors.forename: C
authors.initials: C
authors.lastname: Zangerle
authors.forename: M
authors.initials: M
authors.lastname: Rogy
authors.forename: W H
authors.initials: WH
authors.lastname: Hörl
authors.forename: G
authors.initials: G
authors.lastname: Sunder-Plassmann
authors.forename: J
authors.initials: J
authors.lastname: Menzel
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D011817:Rabbits; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D000418:Albumins; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1