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Gliclazide reduces the induction of human monocyte adhesion to endothelial cells by glycated albumin
Author(s) -
Desfaits A. C.,
Serri O.,
Renier G.
Publication year - 1999
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.1999.00012.x
Subject(s) - monocyte , cell adhesion molecule , gliclazide , cell adhesion , glycation , intercellular adhesion molecule 1 , chemistry , albumin , adhesion , endothelial stem cell , vcam 1 , biochemistry , microbiology and biotechnology , in vitro , immunology , medicine , cell , biology , receptor , insulin , organic chemistry
Summary 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‐κB. Results : Exposition of human ECs for 1–48 h to 100 μg/ml glycated albumin led to a time‐dependent increase in human monocyte adhesion to endothelium. Pretreatment of ECs with 10 μg/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‐κB 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‐κB activation. These results suggest that gliclazide may be beneficial in the prevention of endothelial disturbances associated with hyperglycemia in diabetic patients.