Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products
- 8 May 2003
- journal article
- fj express-summarie
- Published by Wiley in The FASEB Journal
- Vol. 17 (10), 1289-1291
- https://doi.org/10.1096/fj.02-0490fje
Abstract
Endothelial damage is believed to play a key role in the development of both micro- and macrovascular disease in diabetes, and advanced glycation end products (AGEs) may contribute importantly to this. To determine whether glucose-derived AGEs can cause endothelial dysfunction, we examined the effects of albumin AGE-modified by glucose (AGE-Glu) both in vivo, after injection into rabbit femoral artery, and in vitro on rabbit aortic rings and cultured human umbilical vein endothelial cells (HUVEC). Exposure of blood vessels to AGE-Glu, in vivo and in vitro, inhibited endothelium-dependent vasorelaxation, whereas unmodified albumin did not. In isolated rabbit aorta, this effect was reversible after AGE-Glu washout, and the response to the endothelium-independent vasodilator sodium nitroprusside was unaffected by AGE-Glu. In HUVEC, AGE-Glu inhibited endothelial nitric oxide synthase activity, and this was associated with a decrease in serine phosphorylation of this enzyme. Longer term (72 h) incubation decreased HUVEC viability. Use of specific antibodies demonstrated that these effects were mediated by N(epsilon)-(carboxymethyl)lysine (CML), an important AGE found in vivo, and by the AGE-R1 receptor. Furthermore, these effects all occurred at CML concentrations similar to those found in the plasma of diabetic patients. These results suggest an important role of AGE in the pathogenesis of diabetic vasculopathy.Keywords
This publication has 54 references indexed in Scilit:
- Scavenger Receptor Class B Type I-mediated Reverse Cholesterol Transport Is Inhibited by Advanced Glycation End ProductsOnline Journal of Public Health Informatics, 2001
- Role of galectin-3 as a receptor for advanced glycosylation end productsKidney International, 2000
- Characterization of the Advanced Glycation End-Product Receptor Complex in Human Vascular Endothelial CellsBiochemical and Biophysical Research Communications, 1999
- AMP‐activated protein kinase phosphorylation of endothelial NO synthaseFEBS Letters, 1999
- Diabetes, advanced glycation endproducts and vascular diseaseVascular Medicine, 1998
- Urinary Albumin Excretion and History of Acute Myocardial Infarction in a Cross-Sectional Population Study of 2613 IndividualsEuropean Journal of Preventive Cardiology, 1997
- Advanced glycosylation end products stimulate the growth but inhibit the prostacyclin‐producing ability of endothelial cells through interactions with their receptorsFEBS Letters, 1996
- N.epsilon.-(Carboxymethyl)lysine Is a Dominant Advanced Glycation End Product (AGE) Antigen in Tissue ProteinsBiochemistry, 1995
- Widespread tissue distribution, species distribution and changes in activity of Ca2+‐dependent and Ca2+‐independent nitric oxide synthasesFEBS Letters, 1991
- The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholineNature, 1980