title: Gliclazide reduces the induction of human monocyte adhesion to endothelial cells by glycated albumin.
abstract: OBJECTIVE
  To examine the kinetic of human monocyte adhesion to endothelial cells stimulated by glycated albumin, the contributive role of cell adhesion molecules to this effect, and the effect of gliclazide--an hypoglycemic drug with antioxidant properties--on these parameters.
  
  
  METHODS
  In-vitro experiments performed in the presence and absence of gliclazide consisted of: (1) time-dependent determination of human monocyte adhesion to human endothelial cells (ECs) pre-exposed to glycated albumin; (2) evaluation of adhesion after incubation of ECs with antibodies against cell surface adhesion molecules; and (3) determination of EC surface adhesion molecules and of the activity of the transcription factor NF-kappaB.
  
  
  RESULTS
  Exposition of human ECs for 1-48 h to 100 microg/ml glycated albumin led to a time-dependent increase in human monocyte adhesion to endothelium. Pretreatment of ECs with 10 microg/ml gliclazide significantly decreased the glycated albumin-stimulated monocyte adhesion to these cells. Anti-antibodies against E-selectin (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) also reduced the stimulatory effect of glycated albumin on monocyte adhesion. In glycated albumin-treated ECs, an induction of both soluble and cell associated expression of ELAM-1, VCAM-1 and ICAM-1, an augmentation in the levels of these molecule transcripts and an increase in the DNA binding activity for NF-kappaB in the promoters of these antigens were observed. Gliclazide markedly inhibited the induction of all these parameters.
  
  
  CONCLUSIONS
  Glycated albumin stimulates human monocyte adhesion to ECs by inducing cell associated ELAM-1, ICAM-1 and VCAM-1. Gliclazide effectively inhibits monocyte adhesion to ECs by reducing glycated albumin induction of EC adhesion molecules and NF-kappaB activation. These results suggest that gliclazide may be beneficial in the prevention of endothelial disturbances associated with hyperglycemia in diabetic patients.
authors.affiliation: CHUM Research Center, and Department of Nutrition, University of Montreal, Quebec, Canada.
authors.forename: A C
authors.initials: AC
authors.lastname: Desfaits
authors.forename: O
authors.initials: O
authors.lastname: Serri
authors.forename: G
authors.initials: G
authors.lastname: Renier
mesh_terms: D000906:Antibodies / Q000235:genetics / Q000494:pharmacology; D001011:Aorta; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D019040:E-Selectin / Q000276:immunology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D015870:Gene Expression / Q000187:drug effects; D005907:Gliclazide / Q000494:pharmacology*; D017127:Glycation End Products, Advanced; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012709:Serum Albumin / Q000494:pharmacology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D000093423:Glycated Serum Albumin
chemical_list: D000906:Antibodies; D019040:E-Selectin; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D012709:Serum Albumin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005907:Gliclazide; D000093423:Glycated Serum Albumin