α-Lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products

1999 ◽  
Vol 96 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Thomas KUNT ◽  
Thomas FORST ◽  
Axel WILHELM ◽  
Hans TRITSCHLER ◽  
Andreas PFUETZNER ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lipoic Acid ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Advanced Glycation ◽  
Vascular Cell ◽  
Glycation End Products ◽  
End Products ◽  
Cell Adhesion Molecule 1

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.

scholarly journals Fructose causes endothelial cell damage via activation of advanced glycation end products–receptor system

2019 ◽  
Vol 16 (6) ◽  
pp. 556-561 ◽  
Author(s):  
Ami Sotokawauchi ◽  
Takanori Matsui ◽  
Yuichiro Higashimoto ◽  
Sho-ichi Yamagishi
Keyword(s):  
Advanced Glycation End Products ◽  
Cell Adhesion Molecule ◽  
Umbilical Vein ◽  
Reactive Oxygen Species Generation ◽  
Vascular Cell Adhesion ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Umbilical Vein Endothelial Cells ◽  
Cell Adhesion Molecule 1

Objective: Advanced glycation end products and their receptor – RAGE – in the adipose tissues contribute to metabolic derangements in fructose-fed rats. However, it remains unclear whether fructose could cause endothelial cell damage via the activation of AGE-RAGE. Methods: Intracellular advanced glycation end products were evaluated by dot blot analysis. Fructose-derived advanced glycation end products (Fruc-AGEs) were prepared by incubating bovine serum albumin with fructose for 8 weeks. Reactive oxygen species generation was measured using a fluorescent probe. Vascular cell adhesion molecule-1 gene expression was analysed by reverse transcription-polymerase chain reaction. Binding affinities of Fruc-AGEs to DNA-aptamer raised against Fruc-AGEs (Fruc-AGE-aptamer) or RAGE were measured with a quartz crystal microbalance. Results: Fructose increased the advanced glycation end product–specific fluorescence intensity in assay medium, while it stimulated intracellular formation of advanced glycation end products in human umbilical vein endothelial cells. Furthermore, 0.3 mM fructose for 4 days significantly increased reactive oxygen species generation and vascular cell adhesion molecule-1 gene expression in human umbilical vein endothelial cells. Fruc-AGE-aptamer, but not Control-aptamer, bound to Fruc-AGEs with Kd value of 5.60 × 10−6 M and dose-dependently inhibited the binding of Fruc-AGEs to RAGE. Moreover, Fruc-AGE-aptamer prevented the Fruc-AGE- and fructose-induced reactive oxygen species generation and vascular cell adhesion molecule-1 gene expression in human umbilical vein endothelial cells. Conclusion: This study suggests that fructose may elicit endothelial cell damage partly via the activation of AGE-RAGE axis.

Relationship between vascular cell adhesion molecule-1 (VCAM-1), soluble receptor for advanced glycation end products (sRAGE) and functional hemodynamic parameters of arteriovenous fistula

2020 ◽  
pp. 112972982097626
Author(s):  
Maria Ticala ◽  
Crina Claudia Rusu ◽  
Diana Moldovan ◽  
Alina Ramona Potra ◽  
Dacian Calin Tirinescu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Arteriovenous Fistula ◽  
Advanced Glycation End Products ◽  
Cell Adhesion Molecule ◽  
Soluble Receptor ◽  
Vascular Cell Adhesion ◽  
Advanced Glycation ◽  
Vascular Cell ◽  
Glycation End Products ◽  
End Products

Background: The preferred vascular access for hemodialysis is represented by arteriovenous fistula (AVF) due to fewer complications and more prolonged survival. Considerable efforts have been made to identify biomarkers associated with AVF dysfunction, but results are conflicting. Vascular cell adhesion molecule (VCAM-1) and advanced glycation end products are involved in atherogenesis, vascular calcification, peripheral artery disease, and neointimal hyperplasia in renal and non-renal patients. The objective of this study was to evaluate whether there is an association between VCAM-1, soluble receptor for advanced glycation end products (sRAGE), NcarboxymethylLysine (CML), and arteriovenous fistula dysfunction (AVF). Methods: VCAM-1, sRAGE, and CML were performed using the ELISA technique in 88 HD patients. Ultrasound assessment of AVF reports brachial artery blood flow (Qa), brachial resistivity index (RI), presence of calcification, and the diameter. AVF dysfunction was defined as a brachial artery Qa ⩽ 500 ml/min or RI ⩾ 0.5. Results: The median level of VCAM-1 [2676.5(2206.8–4203.9) versus 2613.2(1885.7–3161.8), p 0.026] was significantly higher in patients with AVF dysfunction compared to the rest of the patients. sRAGE and CML were higher in this group but without statistical significance. In patients with AVF dysfunction, significant positive correlations were found between VCAM-1and sRAGE ( r = 0.417, p = 0.001), RI ( r = 0.313, p = 0.046), dialysis vintage ( r = 0.540, p < 0.001), AVF vintage ( r = 0.336, p = 0.032), intima-media thickness ( r = 0.423, p = 0.006) and C-reactive protein ( r = 0.315, p = 0.045). VCAM-1 correlated inversely with cholesterol ( r = −0.312, p = 0.047), triglycerides ( r = −0.358, p = 0.021), body mass index ( r = −0.388, p = 0.012). In multivariate regression analysis, VCAM-1 ( p = 0.013) and sRAGE ( p = 0.01) remained significant predictors of RI and Qa. Logistic regression disclosed calcification, VCAM-1, as risks factors for AVF dysfunction. Conclusion: The results we obtained showed that patients with AVF dysfunction had a significantly higher level of VCAM-l. A positive correlation between VCAM-1 and sRAGE was identified in this group.

scholarly journals Activated endothelium binds lymphocytes through a novel binding site in the alternately spliced domain of vascular cell adhesion molecule-1.

1992 ◽  
Vol 176 (1) ◽  
pp. 99-107 ◽  
Author(s):  
L Osborn ◽  
C Vassallo ◽  
C D Benjamin
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Binding Sites ◽  
Cell Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

Vascular cell adhesion molecule-1 (VCAM-1) is induced on endothelial cells by inflammatory cytokines, and binds mononuclear leukocytes through the integrin very late antigen-4 (VLA-4) (alpha 4 beta 1). This adhesion pathway has been implicated in a diverse group of physiological and pathological processes, including B cell development, leukocyte activation and recruitment to sites of inflammation, atherosclerosis, and tumor cell metastasis. The major form of VCAM-1 (VCAM-7D) has seven extracellular immunoglobulin (Ig)-like domains, of which the three NH2-terminal domains (domains 1-3) are similar in amino acid sequence to domains 4-6. By functional analysis of VCAM-7D relative to VCAM-6D (a minor 6-domain form of VCAM-1 in which domain 4 is deleted because of alternative splicing), and chimeric constructs between VCAM-1 and its structural relative intercellular adhesion molecule-1 (ICAM-1), we show that either the first or the homologous fourth domain of VCAM-1 is required for VLA-4-dependent adhesion. Either of these binding sites can function in the absence of the other. When both are present, cell binding activity is increased relative to monovalent forms of the molecule. The homologous binding regions appear to have originated by internal duplication of a portion of a monovalent ancestral gene, before the mammalian radiation. Thus VCAM-1 exemplifies evolution of a functionally bivalent cell-cell adhesion molecule by intergenic duplication. We have also produced a new class of anti-VCAM-1 monoclonal antibodies that block domain 4-dependent adhesion, and demonstrate that both binding sites participate in the adhesion function of VCAM-1 on endothelial cells in vitro. Therefore both sites must be blocked in clinical, animal, or in vitro studies depending on the use of anti-VCAM-1 antibodies to inactivate the VCAM-1/VLA-4 adhesion pathway.

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