alpha-lipoic acid reduces expression of vascular cell adhesion molecule-I and endothelial adhesion of human monocytes after stimulation with advancedglycation end products

Advanced glycation end products (AGEs) have been identified as relevant med iators of late diabetic complications such as atherosclerotic disease. The endothelial migration of monocytes is one of the first steps in atherogenes is and monocyte-endothelial interaction itself is linked to the express ion of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1). Rec ently, stimulation of VCAM-1 by AG Es has been demonstrated. Since endothel ial stimulation by AGEs is followed by generation of oxygen free radicals w ith subsequent activation of nuclear transcription factor kappa B, we inves tigated the influence of alpha-lipoic acid on the expression of VCAM-1 and monocyte adherence to endothelial cells in vitro by means of cell-associate d chemiluminescence assays and quantitative reverse transcriptase polymeras e chain reaction using a constructed recombinant RNA standard. We found tha t alpha-lipoic acid was able to decrease the number of VCAM-1 transcripts f rom 41.0+/-11.2 to 9.5+/-4.7 RNA copies per cell in AGE-stimulated cell cul tures. Furthermore, expression of VCAM-1 was suppressed in a time- and dose -dependent manner by alpha-lipoic acid as shown by chemiluminescence endoth elial cell assay. Pretreatment of endothelial cells with 0.5 mM or 5 mM alp ha-lipoic acid reduced AGE-induced endothelial binding of monocytes from 22 .5+/-2.9% to 18.3+/-1.9% and 13.8+/-1.8% respectively. Thus, we suggest tha t extracellularly administered alpha-lipoic acid reduces AGE-albumin-induce d endothelial expression of VCAM-1and monocyte binding to endothelium in vi tro. These in vitro results may contribute to the understanding of a potent ial antioxidative treatment of atherosclerosis.