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 κB, we investigated the influence of α-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 α-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 α-lipoic acid as shown by chemiluminescence endothelial cell assay. Pretreatment of endothelial cells with 0.5 ;mM or 5 ;mM α-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 α-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.
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Research Article|
January 01 1999
α-Lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products
Thomas KUNT;
1Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany
Correspondence: Dr T. Kunt.
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Thomas FORST;
Thomas FORST
1Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany
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Axel WILHELM;
Axel WILHELM
1Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany
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Hans TRITSCHLER;
Hans TRITSCHLER
†ASTA Medica, Frankfurt, Germany
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Andreas PFUETZNER;
Andreas PFUETZNER
1Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany
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Oliver HARZER;
Oliver HARZER
1Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany
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Martin ENGELBACH;
Martin ENGELBACH
1Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany
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Albrecht ZSCHAEBITZ;
Albrecht ZSCHAEBITZ
*Institute of Anatomy, University of Mainz, 55131 Mainz, Germany
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Eckart STOFFT;
Eckart STOFFT
*Institute of Anatomy, University of Mainz, 55131 Mainz, Germany
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Juergen BEYER
Juergen BEYER
1Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany
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Publisher: Portland Press Ltd
Received:
June 17 1998
Revision Received:
July 20 1998
Accepted:
August 06 1998
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 1999
1999
Clin Sci (Lond) (1998) 96 (1): 75–82.
Article history
Received:
June 17 1998
Revision Received:
July 20 1998
Accepted:
August 06 1998
Citation
Thomas KUNT, Thomas FORST, Axel WILHELM, Hans TRITSCHLER, Andreas PFUETZNER, Oliver HARZER, Martin ENGELBACH, Albrecht ZSCHAEBITZ, Eckart STOFFT, Juergen BEYER; α-Lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clin Sci (Lond) 1 January 1998; 96 (1): 75–82. doi: https://doi.org/10.1042/cs0960075
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