© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes
aCNR Institute of Clinical Physiology, Pisa, Italy
bColumbia University, New York, NY, USA
cInstitute of Cardiology and Center for Excellence on Aging, "G. d'Annunzio" University, c/o Ospedale S. Camillo de Lellis, Via Forlanini, 50, I-66100 Chieti, Italy
* Corresponding author. Tel.: +39-0871-41512; fax: +39-0871-402817. Email address: rdecater{at}unich.it
The formation of advanced glycation end products (AGEs) is an important biochemical abnormality that accompanies diabetes mellitus and, likely, inflammation in general. Here we summarize and discuss recent studies indicating that the effects of AGEs on vessel wall homeostasis may account for the rapidly progressive atherosclerosis associated with diabetes mellitus. Driven by hyperglycemia and oxidant stress, AGEs form to a greatly accelerated degree in diabetes. Within the vessel wall, collagen-linked AGEs may "trap" plasma proteins, quench nitric oxide (NO) activity and interact with specific receptors to modulate a large number of cellular properties. On plasma low density lipoproteins (LDL), AGEs initiate oxidative reactions that promote the formation of oxidized LDL. Interaction of AGEs with endothelial cells as well as with other cells accumulating within the atherosclerotic plaque, such as mononuclear phagocytes and smooth muscle cells (SMCs), provides a mechanism to augment vascular dysfunction. Specifically, the interaction of AGEs with vessel wall components increases vascular permeability, the expression of procoagulant activity and the generation of reactive oxygen species (ROS), resulting in increased endothelial expression of endothelial leukocyte adhesion molecules. AGEs potently modulate initiating steps in atherogenesis involving blood-vessel wall interactions, triggering an inflammatory-proliferative process and, furthermore, critically contribute to propagation of inflammation and vascular perturbation in established disease. Thus, a better understanding of the biochemical mechanisms by which AGEs contribute to such processes in the vessel wall could be relevant to devise preventive and therapeutic strategies for diabetic atherosclerosis.
KEYWORDS Advanced glycation end products; Atherosclerosis; Inflammation; Diabetes; Endothelium
Time for primary review 16 days
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