Gliclazide reduces the induction of human monocyte adhesion to endothelialcells by glycated albumin

Citation
Ac. Desfaits et al., Gliclazide reduces the induction of human monocyte adhesion to endothelialcells by glycated albumin, DIABET OB M, 1(2), 1999, pp. 113-120
Citations number
23
Categorie Soggetti
Endocrynology, Metabolism & Nutrition
Journal title
DIABETES OBESITY & METABOLISM
ISSN journal
14628902 → ACNP
Volume
1
Issue
2
Year of publication
1999
Pages
113 - 120
Database
ISI
SICI code
1462-8902(199903)1:2<113:GRTIOH>2.0.ZU;2-G
Abstract
Objective: To examine the kinetic of human monocyte adhesion to endothelial cells stimulated by glycated albumin, the contributive role of cell adhesi on molecules to this effect, and the effect of gliclazide-an hypoglycemic d rug with antioxidant properties-on these parameters. Methods: In-vitro experiments performed in the presence and absence of glic lazide consisted of: (1) time-dependent determination of human monocyte adh esion to human endothelial cells (ECs) pre-exposed to glycated albumin; (2) evaluation of adhesion after incubation of ECs with antibodies against cel l surface adhesion molecules; and (3) determination of EC surface adhesion molecules and of the activity of the transcription factor NF-kappa B. Results: Exposition of human ECs for 1-48 h to 100 mu g/ml glycated albumin led to a time-dependent increase in human monocyte adhesion to endothelium . Pretreatment of ECs with 10 mu g/ml gliclazide significantly decreased th e glycated albumin-stimulated monocyte adhesion to these cells. Anti-antibo dies against E-selectin (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1 ) and intercellular adhesion molecule-1 (ICAM-1) also reduced the stimulato ry effect of glycated albumin on monocyte adhesion. In glycated albumin-tre ated ECs, an induction of both soluble and cell associated expression of EL AM-1, VCAM-1 and ICAM-1, an augmentation in the levels of these molecule tr anscripts and an increase in the DNA binding activity for NF-kappa B in the promoters of these antigens were observed. Gliclazide markedly inhibited t he 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-kappa B activation. These results suggest tha t gliclazide may be beneficial in the prevention of endothelial disturbance s associated with hyperglycemia in diabetic patients.