Article
Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products.
Department of Endocrinology, Langenbeckstr. 1, University of Mainz, 55131 Mainz, Germany.
Clinical Science (impact factor:
4.61).
02/1999;
96(1):75-82.
pp.75-82
Source: PubMed
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Citations (0)
- Cited In (8)
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Article: Selenium inhibits high glucose- and high insulin-induced adhesion molecule expression in vascular endothelial cells.
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ABSTRACT: Initiation of an atherosclerotic lesion requires endothelial expression of adhesion molecules. Selenium (Se), a biologically essential trace element, can inhibit cytokine (e.g., TNF-alpha)-induced expression of adhesion molecules. Atherosclerosis is accelerated in diabetic patients. This is at least partially caused by hyperglycemia and hyperinsulinemia increasing adhesion molecule expression. These experiments tested whether Se can also alter high glucose- and high insulin-induced expression of adhesion molecules. Human umbilical vein endothelial cells (HUVECs) were pretreated with Se and stimulated by high glucose or high insulin. Expression of adhesion molecules was measured by Western blot. Se (100 nmol/L) significantly inhibited glucose (25 mmol/L)-induced expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. Moreover, Se significantly inhibited insulin (100 nmol/L)-induced VCAM-1 and ICAM-1 expression, whereas high insulin had no inducing effect on E-selectin. Se also inhibited high glucose- and high insulin-induced activation of p38 mitogen-activated protein kinase (p38), which indicated that the preventive effects of Se on adhesion molecules may be associated with p38. The important role of p38 in Se effects was further confirmed using p38 inhibitor SB203580. These results suggest that Se can inhibit high glucose- and high insulin-induced expression of adhesion molecules. Such antagonism is at least partially mediated through the modulation of p38 pathway. Therefore, Se may be considered as a potential preventive intervention for diabetes-accelerated atherosclerosis.Archives of Medical Research 06/2008; 39(4):373-9. · 1.88 Impact Factor -
Article: The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.
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ABSTRACT: Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.Cardiovascular Diabetology 11/2008; 7:29. · 3.35 Impact Factor -
Article: Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling.
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ABSTRACT: Abnormal regulation of the inflammatory response is an important component of diseases such as diabetes, Alzheimer's disease and multiple sclerosis (MS). Lipoic acid (LA) has been shown to have antioxidant and anti-inflammatory properties and is being pursued as a therapy for these diseases. We first reported that LA stimulates cAMP production via activation of G-protein coupled receptors and adenylyl cyclases. LA also suppressed NK cell activation and cytotoxicity. In this study we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are mediated by the cAMP/PKA signaling cascade. Additionally, we show that LA oral administration elevates cAMP levels in MS subjects. We determined the effects of LA on IL-6, IL-17 and IL-10 secretion using ELISAs. Treatment with 50 µg/ml and 100 µg/ml LA significantly reduced IL-6 levels by 19 and 34%, respectively, in T cell enriched PBMCs. IL-17 levels were also reduced by 35 and 50%, respectively. Though not significant, LA appeared to have a biphasic effect on IL-10 production. Thymidine incorporation studies showed LA inhibited T cell proliferation by 90%. T-cell activation was reduced by 50% as measured by IL-2 secretion. Western blot analysis showed that LA treatment increased phosphorylation of Lck, a downstream effector of protein kinase A. Pretreatment with a peptide inhibitor of PKA, PKI, blocked LA inhibition of IL-2 and IFN gamma production, indicating that PKA mediates these responses. Oral administration of 1200 mg LA to MS subjects resulted in increased cAMP levels in PBMCs four hours after ingestion. Average cAMP levels in 20 subjects were 43% higher than baseline. Oral administration of LA in vivo resulted in significant increases in cAMP concentration. The anti-inflammatory effects of LA are mediated in part by the cAMP/PKA signaling cascade. These novel findings enhance our understanding of the mechanisms of action of LA.PLoS ONE 01/2010; 5(9). · 4.09 Impact Factor
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Keywords
adhesion molecules
Advanced glycation end products
AGE-albumin-induced endothelial expression
AGE-induced endothelial binding
AGE-stimulated cell cultures
alpha-lipoic acid
cell-associated chemiluminescence assays
chemiluminescence endothelial cell assay
diabetic complications
endothelial cells
endothelial migration
first steps
monocyte binding
monocyte-endothelial interaction
nuclear transcription factor kappaB
oxygen free radicals
potential antioxidative treatment
quantitative reverse transcriptase polymerase chain reaction
relevant mediators
vascular cell adhesion molecule-1
