title: [Advanced glycation endproducts: implications for accelerated atherosclerosis in diabetes].
abstract: The formation of advanced glycation endproducts (AGEs) is an important biochemical abnormality accompanying 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. 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 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. The interaction of AGEs with endothelial, as well as with other cells accumulating within the atherosclerotic plaque, such as mononuclear phagocytes and smooth muscle cells, provides a mechanism to augment vascular dysfunction. Specifically, the interaction of AGEs with vessel wall component increases vascular permeability, the expression of procoagulant activity and the generation of reactive oxygen species, 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.
authors.affiliation: Istituto di Fisiologia Clinica, CNR, Pisa.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Basta
authors.forename: Serena
authors.initials: S
authors.lastname: Del Turco
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic