Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products.
Advanced glycation end products (AGEs) have been identified as relevant mediators of late diabetic complications such as atherosclerotic disease. The endothelial migration of monocytes is one of the first steps in atherogenesis and monocyte-endothelial interaction itself is linked to the expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1). Recently, stimulation of VCAM-1 by AGEs has been demonstrated. Since endothelial stimulation by AGEs is followed by generation of oxygen free radicals with subsequent activation of nuclear transcription factor kappaB, we investigated the influence of alpha-lipoic acid on the expression of VCAM-1 and monocyte adherence to endothelial cells in vitro by means of cell-associated chemiluminescence assays and quantitative reverse transcriptase polymerase chain reaction using a constructed recombinant RNA standard. We found that alpha-lipoic acid was able to decrease the number of VCAM-1 transcripts from 41. 0+/-11.2 to 9.5+/-4.7 RNA copies per cell in AGE-stimulated cell cultures. Furthermore, expression of VCAM-1 was suppressed in a time- and dose-dependent manner by alpha-lipoic acid as shown by chemiluminescence endothelial cell assay. Pretreatment of endothelial cells with 0.5 mM or 5 mM alpha-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 that extracellularly administered alpha-lipoic acid reduces AGE-albumin-induced endothelial expression of VCAM-1 and monocyte binding to endothelium in vitro. These in vitro results may contribute to the understanding of a potential antioxidative treatment of atherosclerosis.
Kunt
T
T
Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany.
Forst
T
T
Wilhelm
A
A
Tritschler
H
H
Pfuetzner
A
A
Harzer
O
O
Engelbach
M
M
Zschaebitz
A
A
Stofft
E
E
Beyer
J
J
D000975:Antioxidants / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D008063:Thioctic Acid / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*
D000975:Antioxidants; D017127:Glycation End Products, Advanced; D019010:Vascular Cell Adhesion Molecule-1; D008063:Thioctic Acid