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

被引:20
|
作者
Desfaits, AC
Serri, O
Renier, G
机构
[1] Notre Dame Hosp, CHUM Res Ctr, Metab Unit, Montreal, PQ H2L, Canada
[2] Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada
来源
DIABETES OBESITY & METABOLISM | 1999年 / 1卷 / 02期
关键词
monocyte adhesion; advanced glycation end products; adhesion molecule; gliclazide;
D O I
10.1046/j.1463-1326.1999.00012.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-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 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-kappa B 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-kappa B activation. These results suggest that gliclazide may be beneficial in the prevention of endothelial disturbances associated with hyperglycemia in diabetic patients.
引用
收藏
页码:113 / 120
页数:8
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